X Genetix Granted U.S. Patent for Robotic Platform lab world · Stem Cell Technology ....1 X USPTO Final Ruling Up-holds Remaining Wisconsin Stem Cell Patents.....4 X German Firm

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Vol. 2 March 2008 No. 3

New Cell-Sorting System Devised........................... 1

Applied Biosystems Ad-vances Cell-Based Gene Expression Research ..... 9

Stem Cell lab worldMONITORING NEW TECHNOLOGIES, EQUIPMENT, SUPPLIES, AND SERVICES FOR THE STEM CELL RESEARCH COMMUNITY

PUBLISHED MONTHLY WITH THE STEM ● CELL● RESEARCH● BUYER’S● GUIDE

New CellNew Cell--Sorting System DevisedSorting System Devised

C apitalizing on a cell’s ability to roll along a surface, MIT re-

searchers have developed a simple, inexpensive system to sort different kinds of cells, a process that could result in low-cost tools to test for diseases such as cancer, even in re-mote locations.

Rohit Karnik, an MIT assis-tant professor of mechanical engi-neering and lead author of a paper on the new finding appearing this week in the journal Nano Letters, said the cell-sorting method was minimally invasive and highly inno-vative.

“It’s a new discovery,” Karnik said. “Nobody has ever done anything like this before.”

The method relies on the way cells sometimes interact with a surface (such as the wall of a blood vessel) by rolling along it. In the new device, a surface is coated with lines of a material that interacts with the cells, making it seem sticky to specific types of cells.

The sticky lines are oriented diagonally to the flow of cell-containing fluid passing over the surface, so as certain kinds of cells respond to the coating they are

Industry ResearchIndustry Research Drug Developers May Drug Developers May Realize Big Savings Realize Big Savings From Stem Cell Tech-From Stem Cell Tech-nologynology

F alse positives from animal tests that hide the ineffectiveness or

adverse side effects of new drugs could be avoided with pre-clinical tests using stem cell technologies, potentially saving drug developers millions, according to a report from Kalorama Information.

More than 90 percent of drugs entering clinical development

fail to get to market, due to the lack of effectiveness or adverse side ef-fects not detected in animal tests.

The discovery and commer-cialization of a new drug costs in excess of $1 billion and requires more than 14 years.

Early toxicity testing is a particular problem, since there are

(Continued on page 7)

Drug Developers May Realize Big Savings From Stem Cell Technology .... 1

USPTO Final Ruling Up-holds Remaining Wisconsin Stem Cell Patents...........4

German Firm Said White Blood Cell-Based Technology Offers Alternative To Stem Cells ................................7

BioForce Nanosciences Launches Custom Molecular Printing..........................5

Genetix Granted U.S. Patent for Robotic Platform Imaging........................... 4

nudged to one side, allowing them to (Continued on page 3)

Rohit Karnik

Invitrogen Offers New Animal Origin Free Foam Reduction Agent ............. 11

BioForce Nanosciences Launches Nano eNabler CB For Cellular Biology Re-search ...........................11

CryoPort Launches Pilot Programs For Shipping Stem Cells ............................. 12

New Products For Cold Storage Of Embryos Ap-proved In Canada .......... 12

Table of Contents .......3

2


March 2008 Stem Cell Lab World

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be separated out. Cancer cells, for example, can be separated

from normal cells by this method, which could ultimately lead to a simple device for cancer screening.

Stem cells also exhibit the same kind of selective response, so such devices could eventu-ally be used in research labs to concentrate these cells for further study.

Normally, it takes an array of lab equip-ment and several separate steps to achieve this kind of separation of cells.

This can make such methods impractical for widespread screening of blood samples in the field, especially in remote areas.

“Our system is tailor-made for analysis of blood,” Karnik said.

In addition, some kinds of cells, including stem cells, are very sensitive to external condi-tions, so this system could allow them to be con-centrated with much less damage than with con-ventional multi-stage lab techniques.

“If you’re out in the field and you want to diagnose something, you don’t want to have to do several steps,” Karnik said.

With the new system, “you can sort cells in a very simple way, without processing.”

Now that the basic principle has been har-nessed in the lab, Karnik said, it may take up to two years to develop into a standard device that could be used for laboratory research purposes.

Because of the need for extensive testing, development of a device for clinical use could take about five years.

Karnik worked with six researchers: MIT Institute Prof. Robert Langer, Jeffrey Karp of the Harvard-MIT Division of Health Sciences and Technology, Seungpyo Hong, Ying Mei and Hua-nan Zhang of MIT’s Department of Chemical En-gineering, and Daniel Anderson of the Center for Cancer Research.

The work was funded by a grant from the National Institutes of Health.

Contact: Rohit Karnik, 617-324-1155, [email protected]

-=0=-



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Thermo Fisher Scientific Introduces Break-through In RNA-Interference Technology..........13 Bar Harbor BioTechnology Launches New Line StellARrays........................................................13 Millipore, Guava To Create Integrated Solutions For Flow Cytometry ...........................................14 Harvest Tech Picks Distributor For Bone Regen-eration Product ..................................................15 Invitrogen, Genisphere To Offer New MicroRNA Labeling, Detection Kits.....................................15 Sangamo, Sigma-Aldrich Publish Study Of Zinc Finger Technology, “Knock-Out” Cell Lines.......16 WaferGen Signs Distribution Agreement For SmartSlide Micro-Incubation System ................17 Advanced Cell Technology Announces Catheter Supply Agreement.............................................19 Stem Cell Research News Monthly Recap ......20

Also in this issue...

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PatentsPatents USPTO Final Ruling Upholds USPTO Final Ruling Upholds Remaining Wisconsin Stem Remaining Wisconsin Stem Cell PatentsCell Patents

I n final rulings that cannot be appealed, the U.S. Patent

Office has upheld the remain-ing two claims of the Wiscon-sin Alumni Research Founda-tion (WARF) on its most im-portant human embryonic stem cell patents.

The USPTO had upheld in late February the claims of a key human embryonic stem cell patent (patent “913,” U.S. Pat. 7,029,913), held by WARF (Madison, Wis.).

The Patent Office rejected the arguments made by the two groups that requested the re-examination, finding the expert declarations they submitted to be “flawed by hindsight reasoning.”

But the Foundation for Taxpayer and Con-sumer Rights (FTCR) and the Public Patent Foun-dation (PUBPAT), the two consumer groups con-testing WARF’s stem cell patents, said on Febru-ary 28 that a “closer analysis” of the Patent Of-fice’s decision revealed some substantive “gains” for stem cell researchers.

The claims of the patent cover replicating

cultures of human embryonic stem cells. The long-running controversy turns on the

question of whether Univ. of Wisconsin-Madison Prof. James Thomson’s discoveries in the human embryonic stem cell field were completely origi-nal, and thus patentable, or were simply refine-ments of prior findings.

“The Patent Office has conducted a thoughtful and thorough review of all three pat-ents and we applaud this final decision on our two most important base stem cell patents,” Carl Gul-brandsen, managing director of WARF, said in a

statement. “Dr. Thomson’s groundbreaking work already has led to additional scientific break-throughs and this latest ruling affirms that his pio-neering discoveries are patentable inventions.’’

The latest decision affects two patents for primate and human embryonic stem cells known as “780” and “806” (U.S. Pats. 5,843,780 and 6,200,806).

Contact: http://www.warf.org

-=0=- Genetix Granted U.S. Patent Genetix Granted U.S. Patent for Robotic Platform Imagingfor Robotic Platform Imaging

B oston, Mass.-based Genetix Group plc (AIM:GTX) said on March 6 the U.S. Patent

Office has granted a patent covering a number of important features that include the integration of imaging capabilities into Genetix robotic plat-forms, most notably the ClonePix FL.

It also provides Genetix with intellectual property rights in the U.S. market for robots with integrated optics for single and multi-wavelength excitation and spectroscopic analysis of cells and cell colonies.

The new patent covers the use of spectro-scopic measurements, such as fluorescence, to identify cells and colonies that produce biophar-maceutical proteins including: – secreted proteins such as therapeutic antibodies measured by the addition of a fluorescent probe – membrane bound proteins detected by fluores-cent antibody or ligand – fluorescent proteins within the cell In addition, the patent (No. 7,310,147) covers the use of various pin types to aspirate and pick cells and colonies identified upon the basis of the spec-troscopic measurements.

“We’re delighted to have been granted the ‘147 patent, it covers a number of aspects of our technology within the field of cellular biology,” said CSO Julian F. Burke, Ph.D. “These technolo-gies enable Genetix’ customers to identify cell lines for therapeutic antibody production and iden-



James Thomson

5


tify and isolate stem cells. It is also complemen-tary to our activities within the cell based diag-nostic market.”

Genetix provides products for cell identifi-cation and selection from discovery to diagnosis.

Contact: http://www.genetix.com

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New ServicesNew Services BioForce Nanosciences BioForce Nanosciences Launches Custom Molecular Launches Custom Molecular PrintingPrinting

A mes, Iowa-based BioForce Nanosciences Holdings, Inc. (BFNH) said on March 27

that it is launching a surface patterning service using its Nano eNabler and Nano eNabler CB molecular printers.

The molecular printers provide research-ers with the capability to print tiny domains of biological materials on surfaces with nanometer spatial precision.

The Surface Patterning Service will allow researchers to outsource their molecular printing needs to BioForce while benefiting from the pre-cision and flexibility of the Nano eNabler line of products.

Popular applications of these patterned surfaces include tissue engineering, stem cell re-



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search, and ultra-sensitive biomarker assaid. “This service will target customers with a

need for patterned surfaces but who have limited budgets,” said CEO Kerry Frey. “BioForce will use our Nano eNabler molecular printer to pro-duce surfaces onto which proteins and nucleic acids have been deposited based upon a customer-defined pattern. As this custom service matures BioForce expects to develop a standard catalog of the most frequently requested biomolecular pat-terns.”

“This extends BioForce’s revenue streams to include service as well as sales of our research devices and consumables. We believe that custom patterned surfaces will also give biological re-search institutions a taste of what our technology can do and that this will yield greater demand for the Nano eNabler and Nano eNabler CB.”

“We have been working on the expansion of our market offerings and have become con-vinced that there is a substantial market for this service,” said product manager Michael Lynch. “It is similar to photography in the days when film cameras were the standard; some people had their own dark room, but most of us outsourced our printing needs to a photographic lab. Along came the Polaroid, and then digital cameras and now everyone can make their own color prints at home. As we drive forward to make the Nano eN-abler family of printers easier to use and less ex-pensive, as in the case of our new Nano eNabler CB, we anticipate that more individual research-ers will buy their own instrument. We have ex-panded our sales capabilities to address that con-tingency.”

BioForce Nanosciences creates products and solutions for the life sciences by integrating biological and mechanical systems at the micro and nano scales.

Contact: http://www.bioforcenano.com

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(Continued from page 5)

Stem Cell Lab World March 2008


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currently no good models for determining whether a drug will be toxic in humans.

Some unsafe products advance through testing and approval, only to be pulled from the market later at a huge expense, as was the case with Vioxx and Bextra.

Though stem cell-based drug development technologies are in an early stage of development, and will most likely not become available before 2012 at the earliest, their prospects are promising.

“The excitement around stem cells has un-derstandably been in the potential for therapy, but drug development is where they may have the most impact on healthcare,” said publisher Bruce Carlson. “Stem cell technology could provide a virtually endless supply of liver or heart cells for testing, saving developers tens, if not hundreds of millions of dollars in direct testing fees, as well as indirect costs related to drug recalls.”

Recognizing stem cells’ potential, GlaxoSmithKline, AstraZeneca and Roche estab-lished a new venture in 2007, Stem Cells for Safer Medicines Ltd., to develop effective ways of using human ES cells to screen for potentially dangerous side effects of new drugs before they go into clinical trials.

Contact: “Stem Cells: Worldwide Markets for Transplantation, Cord Blood Banking and Drug Development” can be purchased by visiting http://www.kaloramainformation.

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TechnologiesTechnologies German Firm Said White German Firm Said White Blood CellBlood Cell--Based Technology Based Technology Offers Alternative To Stem Offers Alternative To Stem CellsCells

A German company said on March 5 that it has patented a technology in which mature

white blood cells, or monocytes, extracted from veins can be turned into cells with programmable properties comparable to those of stem cells and differentiated into different functional cells for di-verse applications in diagnostics and therapy.

Blasticon Biotechnologische Forschung GmbH (Kiel, Germany) also said it has products that will soon be introduced to the market.

“We work with mononuclear cells, which can simply be extracted from blood,” said Prof. Dr. Med. Fred Fändrich, director of the Clinic for General Surgery and Thoracic Surgery at the Uni-versity Clinic of Schleswig-Holstein, and founder of the company. “In the second step of our pat-ented procedure we can ‘reprogram’ these pro-grammable cells into the desired target cells, for example liver or muscle cells or cells in pancre-atic islets of Langerhans.”

The therapeutic possibilities lie in replac-ing defective or missing cells (regenerative medi-cine) or producing cells that regulate the immune


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system, the company said. If true, the technology represents a signifi-

cant advancement in the treatment of autoimmune diseases and in transplant medicine.

The “reprogrammed” cells can be used both as diagnostic agents or for therapeutic pur-poses, according to the company.

The company said the main therapeutic targets include inflammatory bowel diseases (morbus Crohn, colitis ulcerosa), diabetes, rheu-matism, cardiac infarction, liver diseases and kid-ney and liver transplants.

Blasticon said its therapeutic agents are for the most part in advanced stages of preclinical or clinical phases of development.

“In most cases, the medical fields of appli-cation described necessitate costly lifelong treat-ment,” the company said in a statement. “Blasticon’s reprogrammed cells make it possible to attack illnesses at their origin and to prevent long duration of treatment. A further possible positive effect of the technologies is significant cost-reduction in the health system.”

Among the products being readied for commercialization, the company said, is the diag-nostic application of the in vitro acute toxicity test “NeoHeps.

The company said that product will be in-troduced as soon as it has been successfully vali-dated by the European Union (EU).

The REACH program, a new EU chemical regulation that went into effect in June 2007, “ is of particular importance here,” the company said.

“It will in future oblige all manufacturers, importers and users of chemicals to evaluate their substances as being safe,” the company said. “Up to now, Blasticon’s ‘NeoHeps’ test system has passed all necessary tests within the EU test framework and has therefore been able to secure itself a clear market lead. In addition, ‘NeoHeps’ could be of considerable benefit to the pharma-ceutical industry, for example in examining the effectiveness and undesirable side effects of medicines. The advantages are less animal test-ing, unlimited availability of the required cells and cost-reduction in the area of drug develop-ment.”

Fändrich belittled the potential of embry-



onic stem cells as a basis for therapeutics. “Personally, I do not think much of the

use of embryonic cells for clinical application,” Fändrich said. “Pure research and clinical re-search should be kept separate from one another. Embryonic stem cells are necessary so that we can gain a better understanding of the program-mability of cells.”

In mid-March the German Bundestag (lower house) will vote on an amendment to the German Stem Cell Act.

Proponents of the amendment are calling for liberalization of stem cell research, while crit-ics favor a general ban on the use of human em-bryonic stem cells.

Blasticon is active in the fields of cellular medicine and in vitro diagnostics.

The company was founded in 2002. Contact: http://www.blasticon.de

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ProductsProducts Applied Biosystems Advances Applied Biosystems Advances CellCell--Based Gene Expression Based Gene Expression ResearchResearch

F oster City, Calif.-based Applied Biosystems (ABI) said on March 26 it is launching a fam-

ily of real-time PCR reagent kits that enable re-searchers to more rapidly perform cell-based gene expression research.

The TaqMan Cells-to-CT Kit solutions are chemical reagents that are designed to reduce the amount of time that is typically necessary to pre-pare and analyze RNA from cultured cells using real-time PCR in applications such as siRNA-mediated gene silencing and microRNA analysis.

This family of kits enables expression analysis to be performed directly from cultured mammalian cells derived from a variety of tissue sources, including epithelial cells and stem cells.

Integrating gold-standard TaqMan chem-istry, these kits are part of a complete workflow that has been designed with all the necessary re-


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agents for performing expression analysis and are validated for use with Applied Biosystems’ TaqMan Assaid and Arrays.

These new, streamlined workflows elimi-nate the time-consuming step of RNA purification and reduce the traditionally labor intensive proc-ess of preparing samples to 10 minutes or less, compared to 30-60 minutes when using tradi-tional methods.

These reagents, which are manufactured and validated by Applied Biosystems, are opti-mized for use with the company’s industry-leading real-time PCR instrument systems.

The TaqMan Cells-to-CT kits expand Ap-plied Biosystems’ portfolio of real-time PCR workflows.

They include: – TaqMan Gene Expression Cells-to-CT Kit for gene expression analysis from mRNA. – TaqMan PreAmp Cells-to-CT Kit for preampli-fication of selected targets when using precious or limited samples. – TaqMan MicroRNA Cells-to-CT Kit for mi-croRNA expression analysis. – TaqMan Fast Cells-to-CT Kit (expected to be released May 2008) for gene expression analysis with Fast Real-Time PCR. “The development of these new reagents demon-strates Applied Biosystems’ continued strategic focus on bringing high-quality, application-specific solutions for real-time PCR to market,” said Peter Dansky, president of Applied Biosys-tems’ functional analysis division. “Our custom-ers are continuing to derive new applications for real-time PCR, and we intend to continue to play a leading role in providing them with differenti-ated solutions that are tailored to their specific re-search workflows.”

Real-time PCR is a laboratory method that is widely used in academic and industry laborato-ries to simultaneously detect and determine the amount of nucleic acids present in samples.

Research data generated using these re-agents can help researchers to precisely assess how changes in the amounts of RNA in these cells may contribute to the development of dis-ease, as well as how they relate to biological


processes. For instance, Reproductive Medicine As-

sociates of New Jersey, one of the world’s largest and most experienced centers for infertility treat-ment, utilizes real-time PCR in its research, which focuses on developing new diagnostics and thera-peutics for in-vitro fertilization.

Scientists at the center have developed an innovative procedure for screening all 46 human chromosomes to identify abnormalities in em-bryos, and have begun to determine when stem cells differentiate during pre-implantation embry-onic development.

They are using the TaqMan Gene Expres-sion Cells-to-CT Kit for several projects includ-ing the characterization of single cells in three-day old embryos.

This particular kit allows them to rapidly process RNA and directly analyze it on TaqMan Arrays without purification.

This is a new time saving workflow that is uniquely enabled by the kit. It also eliminates the loss of RNA, which is particularly important for downstream gene expression analysis of single cells.

“The use of real-time PCR is critical to our ability to perform expression analysis on stem cells,” said Dr. Nathan Treff, Ph.D., director of molecular biology at Reproductive Medicine As-sociates of New Jersey. “Using the TaqMan Gene Expression Cells-to-CT Kit and TaqMan Arrays, we have been able to bring efficiencies to our real-time PCR workflow, while increasing the throughput of our lab 10-fold.”

The complete family of TaqMan Cells-to-CT Kit solutions have been extensively tested and validated to work with Applied Biosystems’ line of TaqMan MicroRNA Assaid and TaqMan Gene Expression Assaid and TaqMan Arrays.

Applied Biosystems is a global leader in the development and commercialization of instru-ment-based systems, consumables, software, and services for the life-science market.

The company’s comprehensive line of real-time PCR chemistries and instrument sys-tems includes the Applied Biosystems 7900HT Fast Real-Time PCR System, 7500 Real-Time PCR System, 7500 Fast Real-Time PCR System,


11


7300 Real-time PCR System, StepOne Real-Time PCR System, and StepOnePlus Real-Time PCR System.

Applied Biosystems is developing and marketing instrument-based systems, consum-ables, software, and services.

Contact: http://www.appliedbiosystems.com/c2ct Contact: http://www.appliedbiosystems.com Contact: http://www.applera.com

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Invitrogen Offers New Animal Invitrogen Offers New Animal Origin Free Foam Reduction Origin Free Foam Reduction AgentAgent

C arlsbad, Calif.-based Invitrogen Corporation (IVGN) said on March 24 it has introduced

GIBCO FoamAway Irradiated AOF (Animal Ori-gin Free), a first of its kind sterile, ready-to-use, anti-foaming reagent that contains no components of human or animal origin.

It is being offered in addition to the origi-nal FoamAway Irradiated released in June 2007.

In cell culture, proteinaceous foam is a symptom of the breakdown of proteins in solu-tion.

For processes where cell culture is used to produce proteins for biotherapeutics, diagnostics or other downstream uses, preventing foam for-mation means a higher yield of protein.

In addition, foam in a bioreactor can trap cells, added supplements or other reagents, reduc-ing batch efficiency.

Foam also traps the proteins being pro-duced in the culture, preventing their purification and reducing batch yields.

FoamAway Irradiated AOF eliminates proteinaceous foam in mammalian and microbial cell culture.

Pre-diluted and sterilized through a vali-dated gamma irradiation process, FoamAway Ir-radiated AOF can be quickly added to a foaming culture without spending time and effort prepar-ing the reagent before adding to the bioreactor.

It can be used to prevent foam before it


forms and eliminate existing foam. “Traditional anti-foaming reagents require

costly and labor-intensive pre-processing before use in cell culture,” said Invitrogen’s Jeff Green-berg. “In contrast, FoamAway saves time and ex-pense and allows the customer to skip the often messy processing steps required with many exist-ing anti-foaming reagents. It has the added advan-tage of being animal origin free, facilitating regu-latory acceptance and eliminating the risk of in-troduction of animal-based agents that can cause problems in downstream applications.”

“FoamAway Irradiated AOF again dem-onstrates Invitrogen’s commitment to improving the production workflow by providing products that are part of complete cell system solutions.”

For added convenience, FoamAway Irra-diated AOF is pre-diluted to three percent concen-tration in water for injection and is packaged in versatile media bags that can connect sterilely to most common bioreactors.

FoamAway Irradiated AOF is available in a 500ml bag for small-scale use and evaluation of performance without major expense and also in a 2.5L bag as an affordable method of bulk pur-chase for larger-scale usage.

Contact: http://www.invitrogen.com/foamaway

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BioForce Nanosciences BioForce Nanosciences Launches Nano eNabler CB Launches Nano eNabler CB For Cellular Biology ResearchFor Cellular Biology Research

A mes, Iowa-based BioForce Nanosciences Holdings, Inc. (BFNH) said on March 18

that it has added a new product to its increasing portfolio of market offerings, the Nano eNabler CB, a molecular printer specially adapted to serve the needs of cellular biology researchers.

The tool is similar to its flagship machine, the Nano eNabler molecular printer which allows researchers to print tiny domains of biological materials on surfaces with nanometer special pre-cision.

“This extension of our product line rein-(Continued on page 12)

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forces the value of our flagship product, the Nano eNabler,” said CEO Kerry Frey. “The customized Nano eNabler CB is designed to answer the needs of the cell biology market, for example, in stem cell or cancer research.”

The Nano eNabler CB is the first in a line of new offerings to be introduced to the research market in the next few weeks.

BioForce Nanosciences integrates biologi-cal and mechanical systems at the micro and nano scales.

Contact: http://www.bioforcenano.com

-=0=- CryoPort Launches Pilot CryoPort Launches Pilot Programs For Shipping Stem Programs For Shipping Stem CellsCells

L ake Forest, Calif.-based CryoPort, Inc. (CYRX) said on March 25 that it has suc-

cessfully completed several shipments of stem cells and other biological materials for a number of potential biotech customers using the CryoPort Express Shipper.

Additional shipments will be made to a number of different global locations including Peru, Australia and Canada.

The shipments are all part of pilot pro-grams to showcase the ease of use, the stringent temperature control and strength of the CryoPort Express Shippers.

“We continue to make strides in our intro-duction of the CryoPort Express Shipper,” said CEO Peter Berry. “Our pilot programs continue to expand and add potential clients that we be-lieve over the long term will become ongoing us-ers of the CryoPort Express Shipper.”

CryoPort develops shipping and storage products for use in the rapidly growing global biotechnology and biopharmaceutical cold chain.

Contact: http://www.cryoport.com

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New Products For Cold New Products For Cold Storage Of Embryos Approved Storage Of Embryos Approved In CanadaIn Canada

K ungsbacka, Sweden-based Vitrolife (STO:VITR) has obtained approval from

Health Canada for two more products within the fertility area.

The products are used for so-called vitrifi-cation, rapid freezing and thawing of cleavage embryos (embryos day 2-3 after fertilization).

The two vitrification products that Vitro-life has obtained approval for are RapidVit Cleave och RapidWarm Cleave.

“These are two very important new prod-ucts for us, as the majority of the clinics that freeze embryos do so at the very stage that the products are intended for, day 2-3 after fertiliza-tion,” said VitroLife’s Nils Sellbom. “We are now continuing to work on getting our systems for cold storage out in several markets”

Products for vitrification involve consider-able technological progress and open up new op-portunities within IVF treatment. Vitrification in-volves very rapid freezing, to prevent the forma-tion of ice crystals that otherwise can cut the cells apart.

In IVF fertilization more than 10 oocytes are often taken from the woman.

A number of these are fertilized. The oocytes that are fertilized but not put

back in the woman can then be kept in cold stor-age.

It has been seen in the use of the vitrifica-tion method that survival increases considerably after cold storage.

The chance of achieving a good cumula-tive pregnancy frequency thereby increases for the woman, without her having to undergo new hormone treatment and the removal of more oo-cytes.

In December 2007 Vitrolife gained ap-proval for its first vitrification products, RapidVit Blast and RapidWarm Blast, for rapid freezing and thawing of blastocysts (embryos day 5-7 after fertilization), in Canada.


13


Vitrolife is a biotechnology/medical de-vice group that works with developing, manufac-turing and selling advanced products and systems for the preparation, cultivation and storage of hu-man cells, tissue and organs.

Contact: http://www.vitrolife.com

-=0=- Thermo Fisher Scientific Thermo Fisher Scientific Introduces Breakthrough In Introduces Breakthrough In RNARNA--Interference TechnologyInterference Technology

W altham, Mass.-based Thermo Fisher Scien-tific Inc. (TMO) said on March 10 that it

has has developed a breakthrough gene-silencing tool that greatly simplifies RNA- interference (RNAi) technology and eliminates barriers associ-ated with previous cellular delivery methods.

The advance is expected to accelerate re-search and drug discovery in many important life sciences fields, including neuroscience, immunol-ogy, stem-cell science and oncology.

Thermo Scientific Dharmacon Accell siRNA is a novel form of short- interfering RNA (siRNA) that is absorbed directly by cells without the use of conventional delivery methods such as transfection reagents, viruses or electroporation.

Dharmacon Accell siRNA effectively si-lences genes in all cell types tested to date.

RNAi is a powerful technology used to si-lence, or knock down, target genes and the pro-teins they produce, revealing their role in biologi-cal pathways and disease processes.

Understanding gene function is critical for the development of drugs targeting those genes.

“Previous technologies for delivering siRNA into difficult cell types, such as primary cells, suspension cells, stem cells and neurons, were often ineffective and resulted in high levels of cell death,” said Dr. Ian Jardine, vice president of global research and development for Thermo Fisher Scientific. “Dharmacon Accell is the only siRNA molecule that has been able to penetrate every cell type we have tested – without the need for delivery reagents that can skew experimental results. With Dharmacon Accell siRNA and our Dharmacon SMARTvector shRNA advancement,


scientists now have an effective RNAi tool set for biomedical and pharmaceutical research that will have broad implications for human health.”

Dharmacon Accell siRNA is simply mixed with the optimized Accell delivery media, then added to cultured cells. It is an easy two-step process that saves researchers significant time in their laboratories and avoids the experimental variability caused by toxicity and off-target ef-fects of conventional siRNA delivery methods.

“There is often a narrow window of condi-tions in which conventional siRNA delivery is ef-fective. Dharmacon Accell siRNA achieves highly efficient siRNA delivery for gene silencing without the need for optimization,” Jardine said. “In addition, the elimination of delivery reagents, along with the associated non-specific effects, greatly simplifies the interpretation of RNAi ex-periments.”

Preliminary studies also suggest that long-term silencing of up to 30 days can now be achieved through repeated application of Dhar-macon Accell siRNA – previously not possible with conventional synthetic siRNA reagents.

Thermo Fisher Scientific provides labora-tory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education.

Contact: http://www.thermofisher.com Contact: http://www.thermo.com/dharmacon

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Bar Harbor BioTechnology Bar Harbor BioTechnology Launches New Line Launches New Line StellARraysStellARrays

T renton, Maine-based Bar Harbor BioTech-nology Inc. on March 6 launched a line of

human StellARray products for gene expression research.

This initial offering of 43 different bio-logical pathways for scientists to select from in-cludes many major human diseases.

Configured to perform gene expression or gene copy number experiments these new Real-


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Time PCR arrays are the first of their kind in the field of gene expression research.

“Scientists researching human diseases like obesity, osteoporosis, and Alzheimer’s dis-ease have a new method for detecting subtle changes in how a group of genes are expressed. That could lead to a breakthrough in their re-search,” said Robert Phelps.

In September 2006, Bar Harbor BioTech-nology Inc. spun off from The Jackson Labora-tory taking with it an exclusive license to com-mercialize the Global Pattern Recognition algo-rithm.

Used in conjunction with StellARrays sci-entists can obtain a new way to see small yet sig-nificant changes in gene expression.

“It is very similar to taking an image of the night sky and comparing it to another image taken at a different time. Most of the stars will align. It’s the small shifts or changes that dramati-cally show up that prove to be significant,” said Dan Shaffer, VP of production.

The company has plans to expand its ex-isting product selection of 46 mouse and 43 hu-man Real-Time PCR arrays to include areas of cancer, metabolism, immunology, stem cell, and neurology research.

Since its initial entrance into the gene ex-pression market on October 1, 2007, the company reports selling StellARrays to major research fa-cilities including Harvard Medical School, Na-tional Institute for Health, and Merck Pharmaceu-ticals Inc.

Contact: http://www.bhbio.com

-=0=-

Strategic AlliancesStrategic Alliances Millipore, Guava To Create Millipore, Guava To Create Integrated Solutions For Flow Integrated Solutions For Flow CytometryCytometry

M illipore Corporation (Billerica, Mass.) and Guava Technologies, Inc. (Hayward,

Calif.) on March 4 announced a partnership to de-liver integrated flow cytometry solutions to scien-


tists conducting research in cell biology, includ-ing stem cell research.

The companies will offer scientists supe-rior technical performance, higher quality data, and much greater accessibility to this powerful analytical platform than is currently available.

Flow cytometry is a technique used by sci-entists to measure changes in protein expression in individual cells that may occur as a conse-quence of many important factors such as (stem) cell differentiation, disease, aging, cancer devel-opment, drug treatment, and toxicity.

The combination of Millipore’s and Guava’s capabilities will integrate instrumenta-tion, reagent kits, validated protocols, and techni-cal support to bring the advantages of flow cy-tometry to the bench tops of cell biologists.

“Our partnership with Guava creates the potential for us to fundamentally improve the way that cell biology research is conducted,” said Mil-lipore CEO Martin Madaus. “The combination of Millipore sample prep and reagents with Guava’s instrument platform will create an integrated of-fering, giving scientists a menu of plug and play solutions to help them generate high quality re-sults that advance their research. The collabora-tion allows us to add considerable value to the highly differentiated antibody portfolio and assay development capabilities that came with our Se-rologicals acquisition.”

Under the terms of the partnership, Milli-pore will gain exclusive rights to distribute Guava’s non-clinical instrumentation within de-fined fields in North America, Europe and other countries in Asia. Additionally, Millipore will provide field service for all Guava instrumenta-tion in the same geographies. Millipore will also develop co-branded reagent kits specifically for Guava’s flow cytometers,. Finally, Millipore and Guava Technologies will work together to de-velop a new generation of instrumentation with enhanced performance and functionality.

“Our two companies have a shared vision of making complex cellular analyses accessible to any scientist. Millipore has significant experience and reach among academic and government re-searchers and an extensive network of highly qualified service providers throughout the world,”


15


said Guava CEO Lawrence Bruder. “With Milli-pore as our partner, together we can make this vi-sion a reality and significantly increase our global presence and lower the barriers for cell biologists to adopt flow cytometry as a major research tool.”

Guava developed the first commercially-available micro-capillary flow cytometry system.

Micro-capillary flow cytometers accom-modate smaller sample volumes, generate less waste, have lower operating costs, and are easier to set up and run than traditional flow cytometry instrumentation.

The collaboration with Millipore will now accelerate delivery of this technology directly into the hands of individual life scientists around the world.

The companies plan to launch co-branded products to the market in July 2008.

Guava Technologies, Inc., a privately held biotechnology and medical device company, isa provider of on-demand, easy-to-use single cell analysis systems.

Contact: http://www.guavatechnologies.com Contact: http://www.millipore.com

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Harvest Tech Picks Distributor Harvest Tech Picks Distributor For Bone Regeneration For Bone Regeneration ProductProduct

P lymouth, Mass.-based Harvest Technologies Corp. said on March 13 that it has selected

Eatontown, N.J.-based Osteotech Inc. (OSTE) to distribute its BMAC System in the United States for the orthopedic bone regeneration market.

Harvest’s BMAC (Bone Marrow Aspirate Concentrate) System is a point-of-care device for concentrating a patient’s own (autologous) bone marrow stem cells.

The system derives bone marrow aspirate concentrate, a rich source of autologous adult stem cells, in just 15 minutes.

The scientific literature establishes that successful bone regeneration is a combination of cells, signal proteins and a quality scaffold.

The combination of Osteotech’s biologic


bone regeneration products with Harvest’s BMAC will provide orthopedic surgeons a new powerful tool.

Until the introduction of Harvest’s system, it was difficult to process and concentrate a clini-cally significant dose of adult stem cells from a patient’s bone marrow at the point of patient care within 15 minutes, the company said.

Contact: http://www.harvesttech.com

-=0=- Invitrogen, Genisphere To Invitrogen, Genisphere To Offer New MicroRNA Labeling, Offer New MicroRNA Labeling, Detection KitsDetection Kits

C arlsbad, Calif.-based Invitrogen Corporation (IVGN) on February 27 will become the ex-

clusive provider of fluorescent microRNA mi-croarray labeling kits using Hatfield, Pa.-based Genisphere Inc.’s 3DNA dendrimer signal ampli-fication technology, based on the terms of a new license agreement.

This technology, combined with Invitro-gen’s Alexa Fluor fluorescent dyes, is now com-mercialized in the new NCode Rapid miRNA La-beling System, available from Invitrogen.

Genisphere’s unique 3DNA dendrimer technology, winner of Frost and Sullivan’s 2005 Technology Innovation Award for nucleic acid labeling products for microarrays, is based on highly branched DNA structures serving as scaf-folds for multitudes of fluorescent dyes.

Using the 3DNA dendrimer technology, the NCode Rapid miRNA Labeling System is a fast and reproducible system to directly label mi-croRNAs (ribonucleic acids) with fluorescent Al-exa Fluor tags.

“When working with small nucleic acids, sensitivity is often limited. Our development of a simple process to efficiently couple microRNAs directly to 3DNA dendrimers is a significant im-provement over past methods,” said Dr. Robert Getts, research and development director at Genisphere. “Combining Genisphere’s unique la-beling approach with Invitrogen’s microRNA ar-ray content will provide researchers with a power-


16


ful solution in their investigation of the biology of microRNAs.”

“Our new kit accelerates the discovery of novel microRNA biomarkers by reducing the amount of time scientists must invest to detect microRNAs. In addition, we have increased sensi-tivity compared to alternative technologies, which can preserve precious samples,” said Peter Welch of Invitrogen. “Because microRNAs play a sig-nificant role in cancer and in the differentiation of stem cells, discoveries resulting from experiments in those areas could potentially expedite the diag-nostics applications of microRNA biomarkers in disease.”

Using this new system, scientists can start with a total RNA sample as little as 250 nanograms, eliminating the need to purify the mi-croRNA sample prior to labeling.

Using a single hybridization step (versus the two-step process required by other systems), scientists will be able to complete the experiment in less than eight hours.

The test reliably detects 2-10 copies of mi-croRNA per cell.

“Epigenetic mechanisms, including the ac-tivity of microRNAs, play a critical role in many key areas of biological research,” said Amy But-ler of Invitrogen. “This addition to our epigenetic product portfolio will help scientists more easily advance their research in this rapidly evolving field.”

Genisphere Inc., a subsidiary of Datascope Corp. (Montvale, N.J.), is a manufacturer of kits and reagents used for the ultra-sensitive detection of nucleic acids and proteins.

Contact: http://www.genisphere.com Contact: http://www.invitrogen.com/ncode Contact: http://www.invitrogen.com/epigenetics

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Sangamo, SigmaSangamo, Sigma--Aldrich Aldrich Publish Study Of Zinc Finger Publish Study Of Zinc Finger Technology, “KnockTechnology, “Knock--Out” Cell Out” Cell LinesLines

S t. Louis, Mo.-based Sigma-Aldrich Corpora-tion (SIAL) and Sangamo BioSciences, Inc.

(Richmond, Calif.) on March 24 announced pub-lication of data demonstrating the use of San-gamo’s zinc finger DNA-binding protein nucle-ases (ZFNs) in a new approach for rapid genera-tion of “knock-out” cell lines, important tools in research and therapeutic product development.

This work, which was carried out in col-laboration with scientists from Pfizer Inc., repre-sents a significant advance in the specificity and efficiency of the generation of cell lines in which an individual gene has been “knocked-out” or de-leted.

Such cell lines are powerful tools that are widely used in research to identify a gene’s func-tion, in drug development to screen potential drug candidates and for production of recombinant proteins.

In addition, Sangamo is using this technol-ogy to develop ZFP Therapeutics for the treat-ment of HIV/AIDS and brain cancer.

Sigma-Aldrich is Sangamo’s exclusive li-censee for this technology in the laboratory re-search reagent field.

“These data have broad implications for experimental and translational biology, biotech-nology and medicine,” said Philip Gregory of Sangamo. “The generation of knockouts in basic research and industrial cell line engineering has been severely limited by the absence of efficient methods for the specific, targeted disruption of any gene. Our ZFN technology facilitates this in a rapid, single-step process. Importantly, the proc-ess enables the simultaneous disruption of both cellular copies of the gene of interest with an effi-ciency that obviates the need for selection mark-ers and other complicated strategies to identify knockout cells – a dramatic improvement over ex-isting methodologies.”

The data demonstrate that ZFN technol-(Continued on page 17)

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ogy can be used to significantly speed up the process of generating cell lines in which a single gene is specifically knocked out.

ZFNs were used to place a double strand break in the DNA sequence precisely within the gene to be eliminated.

The process then takes advantage of the cell’s DNA repair system which repairs the break in the sequence.

This natural process often results in a small amount of DNA being deleted at the site of the break and the consequent disruption of the ex-pression of the gene and the protein that it en-codes.

Sangamo and Pfizer scientists demon-strated that the disruption process occurred with sufficiently high frequency that selection markers were not required to identify multiple independ-ent knockout cell lines with minimal screening effort.

“This publication represents ground-breaking work in the use of ZFNs and highlights an application of this powerful technology that is expected to revolutionize research, drug develop-ment, and protein production. Sigma’s aim is to make the technology widely available to scientists throughout the world,” said David Smoller of Sigma-Aldrich. “In addition to reagents for knocking out an investigator’s ‘favorite gene’ in a particular cell type, the ZFN platform can be used to generate panels of cell lines for small molecule drug screening in which the ‘druggable universe’ of gene targets have been individually knocked out. We expect to have ZFN research reagents similar to those used in this publication available to all research scientists in the very near future.”

“The applications of this technology are of significant commercial value,” said Sangamo CEO Edward Lanphier. “While the current publi-cation focuses on research and biotechnology ap-plications, we have used these same techniques for knocking out genes in multiple crop plants and to develop ZFP Therapeutics. We are devel-oping potential treatments for HIV/AIDS by knocking-out the CCR5 gene in T-cells and for brain cancer (glioblastoma) by disrupting the glu-cocorticoid receptor (GR) in engineered killer T-cells. We expect to file Investigative New Drug Applications (INDs) for both of these programs to


enter the clinic later this year.” Sigma-Aldrich biochemical and organic

chemical products and kits are used in scientific and genomic research, biotechnology, pharma-ceutical development, the diagnosis of disease and as key components in pharmaceutical and other high technology manufacturing.

Sangamo BioSciences. is developing novel DNA-binding proteins for therapeutic gene regulation and modification.

Contact: http://www.pnas.org/ (“Targeted Gene Knockout in Mammalian Cells Using Engi-neered Zinc Finger Nucleases”).

Contact: http://www.sangamo.com Contact: http://www.sigma-aldrich.com

-=0=-

WaferGen Signs Distribution WaferGen Signs Distribution Agreement For SmartSlide Agreement For SmartSlide MicroMicro--Incubation SystemIncubation System

F remont, Calif.-based WaferGen Biosystems, Inc. (WGBS) on March 24 announced the

signing of an exclusive distribution agreement for the company’s SmartSlide Micro-Incubation Sys-tem with Labtech International Limited in the United Kingdom and Labtech France in France.

The distributor agreement covers Wafer-Gen’s entire family of SmartSlide Micro-Incubation System products.

Labtech International Limited is a leading provider of innovative scientific products to re-searchers in the life science markets in the United Kingdom, while its sister company, Labtech France, coordinates distribution of the same prod-ucts in France.

WaferGen’s SmartSlide Micro-Incubation System is a first-of-its-kind family of integrated fluidics exchange micro-incubation products that work seamlessly with inverted microscopes.

This breakthrough technology is enabling cell biology and stem cell researchers to conduct complex time lapse imaging studies to character-ize, differentiate and proliferate cells, as well as grow stem, primary and other difficult to cultivate cells in consistently optimal physiological condi-


18


tions. These innovative capabilities will allow

researchers to pursue cutting-edge research topics that are not addressable with existing technology.

“The signing of this important distributor agreement is just the latest in a number of recent key milestones related to our SmartSlide Micro-Incubation System. In just the past six weeks, we have signed distribution agreements covering five critical overseas markets, launched our new SmartSlide 200 Micro-Incubation System, and announced our first SmartSlide 200 customer adoption,” said CEO Alnoor Shivji. “This impres-sive momentum is playing a major role in our on-going efforts to grow our SmartSlide Micro-Incubation System business and we expect to con-tinue to achieve important program milestones throughout the remainder of 2008.”

“As a company that prides itself on pro-viding our customers with the most sophisticated life science instruments available, we are excited to add WaferGen’s SmartSlide Micro-Incubation System to the broad menu of products that we of-fer,” said Labtech CEO Brian Page. “With more than 25 years of personal experience in the cell culture market, I am particularly impressed with the SmartSlide Micro-Incubation System and the innovative research activities the platform en-ables.”

WaferGen has developed and is currently marketing the SmartSlide Micro-Incubation Sys-tem, a first-of-its-kind family of integrated flu-idics exchange micro-incubation products that work seamlessly with inverted microscopes.

This breakthrough technology is enabling cell biology and stem cell researchers to conduct complex time lapse imaging studies to character-ize, differentiate and proliferate cells, as well as grow stem, primary and other difficult to cultivate cells in consistently optimal physiological condi-tions.

These innovative capabilities will allow researchers to pursue cutting-edge research topics that are not addressable with existing technology.

The core element of the SmartSlide Mi-cro-Incubation System is the compact, sterile and disposable SmartSlide-6 Micro-Incubator which is designed to maintain cells at specific physio-logical conditions for prolonged cell or tissue im-


aging. The SmartSlide-6 Micro-Incubator allows

for programmable fluidics exchanging, enabling the delivery of up to six nutrient media and gas into each of its six individual wells in both inter-mittent and continuous perfusion modes.

WaferGen has developed a family of SmartSlide Micro-Incubation System products built upon the SmartSlide-6 Micro-Incubator that offers cell biology and stem cell researchers vary-ing levels of control over specific environmental conditions such as nutrient flow, temperature, hu-midity, gas and pH. Each of these SmartSlide Mi-cro-Incubation System products incorporates easy-to-use graphical interface software that al-lows for complete walk-away automation.

The SmartSlide Micro-Incubation System family of products consists of four currently mar-keted products: SmartSlide 50 Micro-Incubation System, SmartSlide 100 Micro-Incubation Sys-tem, SmartSlide 150 Micro-Incubation System, and SmartSlide 200 Micro-Incubation System.

Since the launch of its SmartSlide Micro-Incubation System in late 2006, WaferGen has seen a positive response from many leading re-search institutions and organizations.

The company’s current SmartSlide Micro-Incubation System customers include Harvard University, Mayo Clinic, Memorial Sloan-Kettering Cancer Center, Abbott Labs, the Na-tional Institutes of Health (NIH), and several leading pharmaceutical companies.

WaferGen Biosystems makes systems for gene expression, genotyping, cell biology and stem cell research for the life science and pharma-ceutical industries.

Contact: http://www.wafergen.com

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Advanced Cell Technology Advanced Cell Technology Announces Catheter Supply Announces Catheter Supply AgreementAgreement

L os Angeles, Calif.-based Advanced Cell Technology, Inc. (ACTC) on March 5 an-

nounced a supply agreement with Biologics De-livery Systems Group, Cordis Corporation (a Johnson & Johnson company), in which Biologics Delivery Systems will supply catheters for the Phase II human clinical trial of ACT’s myoblast therapy for the treatment of heart failure.

Advanced Cell Technology’s myoblast therapy successfully completed Phase I human clinical trials in 2007 utilizing the therapy safely in more than forty patients.

Safety of the therapy was demonstrated in four independent studies.

The U.S. Food and Drug Administration has given the company clearance to proceed with Phase II human clinical trials.

The company expects its Phase II human clinical trial (CAuSMIC II) to begin shortly.

ACT’s myoblast therapy involves the transplantation of expanded autologous myoblasts (adult progenitor stem cells) derived from a small biopsy of skeletal muscle from a patient’s leg.

The technology allows for the expansion of myoblasts into hundreds of millions of cells over a period of two to three weeks.

The resulting myoblasts are then trans-planted back into the patient’s scarred heart tissue through the use of a catheter-based procedure.

Over one million new patients with heart attacks are treated annually in the United States alone, representing a multi-billion dollar market opportunity.

Current therapies do not result in rebuild-ing of heart muscle and do not prevent progres-sion of congestive heart failure, poor quality of life, and long-term deterioration.

According to the National Heart, Lung, and Blood Institute, a division of the National In-stitutes of Health, approximately 5 million people in the United States have congestive heart failure and an estimated 400,000 new cases are diag-nosed each year.

Roughly 50 percent of CHF patients die


within 5 years. The Phase II human clinical trial will be a

multi-center study following a similar protocol to the one used in the company’s Phase I study.

That study demonstrated safety and evi-dence of significant heart function improvement in congestive heart failure patients as a result of the implantation of the

ACT’s proprietary autologous skeletal myoblasts using the Biologics Delivery Systems NOGA Cardiac Navigation System and MyoStar Injection Catheter.

“The NOGA System created highly pre-cise, three-dimensional images of the heart. These images gave us a clear ‘map’ that helped us to successfully deliver the adult stem cells where we intended them to go,” said Dr. Nabil Dib, the lead investigator for the myoblast phase I study. “This imaging technology was critical to making this study possible.”

The Phase II human clinical trial will use the latest generation catheters provided as a result of ACT’s ongoing relationship with the Biologics Delivery Systems.

Contact: http://www.advancedcell.com

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Stem Cell Research News Stem Cell Research News MonthlyMonthly Recap Recap

Abridged from the March 2008 issues of Stem Cell Research News.

sis that target differentiated cells like osteoblasts and the osteoclasts that break down bone have limitations, the ability to direct differentiation of MSCs could be a promising approach to treating osteoporosis and cancer-associated bone loss, the researchers said.

Contact: David Scadden, 617-726-5615, [email protected]

-=0=- Bone Marrow Stem Cell Release Bone Marrow Stem Cell Release Regulated By Brain’s Biological ClockRegulated By Brain’s Biological Clock

T he release of blood stem cells from bone mar-row is regulated by the brain through the cy-

clical human biological clock, via adrenergic sig-nals transmitted by the sympathetic nervous sys-tem, Mount Sinai researchers have discovered.

Published online on February 6 on the Web site of the journal Nature, the study points out that the harvest of stem cells for transplantation may be improved by timing it at the peak of their release.

The study describes the mechanisms at the molecular levels in which signals from the biologi-cal clock in the brain are sent via the sympathetic, or “fight or flight,” branch of the nervous system, directly to bone marrow stem cell niches.

Researchers, using mice as a model, were able to show the rhythmic release and peak of stem cells in circulation during the mouse’s resting pe-riod, and that changes in the light cycle or an ex-perimental “jet lag” altered the release patterns.

This is the first time a study has demon-strated that the brain regulates a stem cell niche.

The vast majority of bone marrow trans-plantation procedures are currently done using stem cells harvested in the peripheral blood.

The current harvesting procedure, however, may not be adequate in some patients, particularly in those that have received prior treatments for cancer.

“What is really amazing to us is that the brain, through the autonomous branch of the nerv-ous system, directly controls stem cells in their mi-croenvironment,” Frenette said. “An important im-plication in today’s busy world is that changes in


Cancer Drug Prompts Adult Stem Cells Cancer Drug Prompts Adult Stem Cells To Become Bone TissueTo Become Bone Tissue

A drug used to treat bone marrow cancer acti-vates stem cells to differentiate into bone

cells (osteoblasts) and may offer a treatment strat-egy for osteoporosis and other degenerative con-ditions, according to a study using mice reported in the March 2008 Journal of Clinical Investiga-tion.

The study by researchers from Massachu-setts General Hospital (MGH) and the Harvard Stem Cell Institute (HSCI) found that a medica-tion used to treat bone marrow cancer improved bone density in a mouse model of osteoporosis, apparently through its effect on the mesenchymal stem cells (MSCs) that differentiate into several types of tissues.

The study was designed to examine whether the drug bortezamib (Bzb), which can al-leviate bone destruction associated with the can-cer multiple myeloma, could also regenerate bone damaged by non-cancerous conditions.

In their first experiments, the researchers showed that treating mice with Bzb increased sev-eral factors associated with bone formation.

Similar results were seen when cultured MSCs were treated with Bzb, but not when the drug was applied to cells that were committed to become particular cell types.

Found in the bone marrow, MSCs have the potential to develop into the bone-building os-teoblasts and several other types of cells, includ-ing cartilage, fat, skin and muscle.

Subsequent experiments supported the hy-pothesis that Bzb increases osteoblast activity and bone formation by acting on MSCs but not on more differentiated osteoblast precursors.

Use of Bzb to treat a mouse model of menopausal osteoporosis produced significant im-provements in bone formation and density.

Because current treatments for osteoporo-

21


normal biological rhythms, for example by work-ing night shifts or a jet lag, could affect the num-ber of stem cells harvested from donors,”

Contact: 212-659-9693, [email protected]

-=0=- Stem Cell Therapy Studies For Stroke, Stem Cell Therapy Studies For Stroke, Cerebral Palsy Prepare For Clinical Cerebral Palsy Prepare For Clinical TrialsTrials

T wo new federally funded studies by research-ers at the Medical College of Georgia will

search for answers about optimal dosage and tim-ing for stem cell therapy in adults with strokes and newborns with ischemic injuries, it was an-nounced on January 29.

According to Dr. Cesario V. Borlongan, neuroscientist at the Medical College of Georgia and Charlie Norwood Veterans Affairs Medical Center, answers to these questions are critical be-fore clinical trials can begin.

Borlongan is principal investigator on the National Institutes of Health grants totaling $6 million that also will explore long-term benefits of cell therapy.

If these additional laboratory studies repli-cate the promising results of the pilot studies, which indicate about a 25 percent improvement in recovery over controls, MCG and VA researchers hope to begin clinical trials in new ischemic inju-ries in adults and children within two years.

“We are looking at different procedures that we can adopt from the laboratory for the clinic,” Borlongan said. “We have at least 10 years of basic research that clearly shows that stem cells have the potential to be a new therapy for adult stroke.”

“This is a whole new paradigm, a totally different way of targeting disease,” said Dr. David Hess, chairman of the MCG Department of Neurology and co-investigator. Clot buster tPA is the only drug that is FDA-approved to treat ischemic strokes; an often-delayed diagnosis and a three-hour treatment window mean only a small percentage of patients get it.

Hess and Borlongan said cell therapy


could eventually be used alone or in conjunction with tPA, if recovery is not sufficient.

Pilot studies indicate cell therapy can be of benefit up to seven days after a stroke but that two days out is the optimal time of delivery.

“This will allow us to enroll patients who get tPA, give us plenty of time to assess them and prepare the cells,” Borlongan said.

Their success in an adult stroke model led the researchers to explore the potential for helping babies recover from hypoxic ischemia, a loss of blood and oxygen that can result in cerebral palsy, broadly defined as a brain injury that occurs be-fore or during birth.

Ischemic brain injury accounts for about 10 percent of cerebral palsy and about 80 percent of strokes.

They found young, developing brains more adaptable to injury and better able to re-cover even without intervention.

“Very young patients may be the biggest beneficiaries of cell therapy,” said Dr. James E. Carroll, chief of the MCG Section of Pediatric Neurology and a co-investigator. “Our hope is that cell therapy will speed recoveries of babies who have experienced a brain injury at birth.

“You want to increase the spontaneous re-covery, enhance the neurogenesis that is already occurring in the brains of these young patients,” Borlongan said.

They have models for mild, moderate and severe ischemic injury to reflect damage that can result from scenarios such as an umbilical cord wrapped around the fetus’ neck or placental ab-ruption, which disrupts the fetus’ source of oxy-gen and nutrients.

Researchers expect that cell therapy likely would be used as an adjunct to hypothermia, a new FDA-approved treatment for hypoxic ischemic injury in babies that appears to improve outcomes by reducing metabolic rates, including oxygen requirements, in the hours following an injury.

Given intravenously, the adult, bone mar-row-derived stem cell line, developed by Cleve-land-based biopharmaceutical company Athersys, Inc., seems to hone in on the area of injury where it works multiple ways.


22


While only a small fraction of the cells ac-tually survive and mature into neurons – more survive in the baby model than the adult – trophic factors they secrete significantly enhance recov-ery of brain cells injured by lack of oxygen and help grow new blood vessels.

Nothing seems to help the core of the ischemic area in stroke, which is formed within hours of injury; even when cells are placed di-rectly into the core, they do not survive in the area, which is devoid of a blood supply, Borlon-gan said.

However the cells and their trophic factors can dramatically reduce the penumbra, the area of damaged cells surrounding the core, an area that can continue to grow several days after injury.

These undifferentiated stem cells don’t seem to interest the immune system, so immuno-suppression is not required as it typically is for organ transplants, even when a human cell is placed in a rat, Borlongan said.

Also, pilot studies that have followed rat models for two months after transplant – a long time considering the average rat lives two years – haven’t found any signs of tumor formation, which is a concern with stem cells.

The new studies will follow transplants for six months, to ensure that efficacy and safety hold up, Borlongan said.

They’ll explore dose ranges between 400,000 and 40 million cells.

“We want to see, if we implant more cells, will it be more beneficial”“ said Borlongan. “It may not be the more the merrier.”

In preparation for clinical trials, the re-searchers already have clinical advisory groups for the studies and have begun submitting grant proposals and talking with the FDA.

Smaller studies in non-human primate models may also be required before clinical trials begin, Borlongan said.

Athersys scientists Robert J. Deans and Robert W. Mays are co-investigators on the stud-ies.

Contact: Cesario V. Borlongan, [email protected]

-=0=-


Carbohydrate Regulates Stem Cell Carbohydrate Regulates Stem Cell PotencyPotency

H eparan sulfate, a carbohydrate molecule that coats certain proteins on the cell surface, is

critical for the proper proliferation and potency of embryonic stem cells, Japanese researchers re-ported on February 1.

Stem cells' tremendous therapeutic poten-tial arises from their ability to continually self-renew and turn into any adult cell type.

Researchers have long been trying to un-cover the basis of these abilities, but while several proteins and growth factors are known to play a role both inside and outside the cell, the molecu-lar mechanisms remain largely unknown.

Many of the stem-cell associated can at-tach to heparan sulfate molecules, so Shoko Ni-shihara and colleagues examined what would happen to mouse stem cells in cell culture if heparan sulfate production was reduced or blocked.

They discovered that three of the major external factors promoting stem cell renewal (proteins called Wnt, FGF, and BMP) could not induce the proper signals inside the cell without heparan sulfate (HS).

As a result, HS deficient cells grew more slowly, and also spontaneously differentiated into other cells more often, at rates that correlated with the level of inhibition.

Nishihara and colleagues propose that heparan sulfate might be the cell-surface compo-nent that mediates the external and internal sig-nals promoting stem cell renewal, and could be an important target for stem cell engineering.

Contact: Shoko Nishihara, Laboratory of Cell Biology, Department of Bioinformatics, Fac-ulty of Engineering, Soka University, Tokyo, Ja-pan; +81-426-91-8140, [email protected]

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23


Researchers Use Stem Cells To Treat Researchers Use Stem Cells To Treat Brittle Bones Disease In The WombBrittle Bones Disease In The Womb

A research team at the Imperial College Lon-don said on January 29 that specially ma-

nipulated stem cells transplanted into 14-day-old mouse fetuses successfully treated brittle bone disease.

The disease affects babies while still in-side the womb.

Collagen, one of the main building blocks for bone, fails to develop properly.

The disease is detected by DNA testing or ultrasound before birth; it leads to weak bones and stunted growth.

However, the disease varies in its impact. A mildly affected child may be suscepti-

ble to fractures, while a severely affected child may suffer multiple fractures in the womb and have little chance of survival.

A child with a third type of OI that exhib-its between the extreme forms may have fractures in the womb, but is more likely to survive past birth.

However, the child’s growth will be stunted and he will suffer multiple, painful frac-tures throughout his life, with each leading to fur-ther deformity.

Such children usually have a shortened life expectancy.

The treated mice showed a reduction in long bone fractures of two thirds, compared with an untreated group, by the time they were twelve weeks old, the scientists reported.

They also found that the bones of the mice were stronger, thicker and longer than those with


the disease that had not received the transplants. The results published in the journal Blood

suggest that, with further research, this treatment could be translated to hu-man babies in pregnancies that are affected by the inherited disease, also known as osteogenesis imperfecta (OI).

The results of such an in utero stem cell procedure could lead to a new treatment for ba-bies with brittle bones, as well as a range of other disabling conditions, according to maternal-fetal medicine researcher Prof. Nicholas Fisk.

Fisk, who now heads the new A$66 mil-lion Centre for Clinical Research at the University of Queensland (UQ), said the work held potential for improving treatment of other disabling condi-tions such as muscular dystrophy and congenital brain diseases.

“Prof. Fisk’s work is a real breakthrough. It suggests that if stem cells could be successfully transplanted before a baby with OI is even born, it could mean a significant improve-ment in the child’s health and quality of life,” said Dr. Yolande Harley of the UK charity Action Medical Research, which funded the project.

Fisk said the research had shown “a pro-found therapeutic benefit” of intrauterine stem cell therapy.

“It has significance not only for treating this and other disabling conditions in affected fe-tuses inside the womb, but also for future related work,” he said. “It will help us to understand what it is that leads to such a marked effect after a sin-gle transplant of stem cells, so that this can be harnessed to improve the results of stem cell ther-apy in repairing adult tissues and degenerative conditions.

“Our work suggests that, in the future, it could be possible to take stem cells from an un-born baby carrying the abnormal OI gene, ma-nipulate them to correct the errant gene and then put them back into the fetus to allow it to develop properly.”

Prof. Fisk and his team investigated mouse models of the form of the disease that falls between the two extremes.

Fetal mesenchymal stem cells were in-jected through the wall of the uterus into 14-day-



24


old fetuses. At three months, treated mice had suffered

just one-third of the long bone fractures compared with untreated mice.

Contact: Nicholas Fisk, +334-65500

-=0=- Researchers Create Stem Cell Lines Researchers Create Stem Cell Lines From Discarded IVF Embryos From Discarded IVF Embryos

H uman embryos that are discarded every day as medical waste from in vitro fertilization

(IVF) clinics could be an important source of stem cells for research, according to a team of re-searchers at Children’s Hospital Boston.

Some of the embryos created during IVF are deemed “clinically useless” because of imper-fections, but a paper published in the January 27 online edition of Nature Biotechnology shows that it is possible to derive stem cell lines from these poor-quality embryos.

“We have definitively shown that those embryos that can’t be used clinically are a reliable source for embryonic stem cell derivation,” said Paul Lerou, M.D., the study’s first author and a neonatologist at Children’s.

Because poor-quality embryos are dis-carded everyday in the course of IVF, the authors believe they represent an ethically acceptable source of stem cells for research.

Typically, half of an average yield of seven embryos per cycle are discarded, providing a potential source of hundreds of thousands of embryos every year.

“It’s a resource that’s out there that we feel should be used,” Lerou said.

An embryonic stem cell line is a popula-tion of cells that can grow and divide indefinitely outside the body, providing a source of cells for scientists conducting stem cell research.

However, these cultured cells begin to change over time, so scientists must create new lines in order to have an ongoing source of cells to study.

Because human embryos are a limited re-source, scientists have been trying to determine how far an embryo must be developed in order to


give rise to a cell line. During the IVF process, specialists work

to identify embryos most likely to yield a healthy baby.

Once an egg is fertilized by sperm, the embryo is allowed to incubate for a few days be-fore being implanted into a woman’s uterus.

During that time, the embryo is evaluated according to a grading system and some are dis-carded if they are poorly shaped or have failed to grow normally.

The current study sheds light on the feasi-bility of creating stem cell lines from IVF em-bryos at different stages of development and of different quality.

The research team attempted to derive stem cell lines from more than 400 poor-quality embryos received from the IVF clinic at the Brig-ham and Women’s Hospital.

Lerou, who is also an instructor in pediat-rics at Harvard Medical School, said that by using such a large sample, the team could statistically calculate how readily embryos at different stages of development gave rise to stem cell lines.

They found that discarded embryos can yield viable stem cell lines, but the efficiency of creating lines depends on the stage of the em-bryo’s development.

From a sample of 171 embryos that were discarded just three days after fertilization, the team was able to derive only one stem cell line, which came from an embryo that had ceased di-viding.

This represents the earliest embryo that had ever yielded a stem cell line.

Most human embryonic stem cell lines are derived from embryos that have become blasto-cysts, usually at about five days after fertilization. The findings suggest that even these “early-arrested” embryos, sometimes called dead embryos, may harbor individual cells capable of growing and dividing.

Earlier reports about creating stem cell lines from early-arrested embryos garnered atten-tion as a way for scientists to use cells from dead embryos in a manner akin to harvesting organs from a person who is determined to be brain-dead, which might be deemed more ethically ac-


25


ceptable. However, the current study shows that the

success rate using early-arrested embryos is a mere 0.6 percent, a number that is too inefficient to be practical for science, according to George Daley, M.D., Ph.D., associate director of the Stem Cell Program at Children’s Hospital Boston and senior author of the study.

The ability to create stem cell lines from discarded embryos rose dramatically in embryos that were slightly more developed.

Embryos discarded from the clinic at day five of their development gave rise to stem cell lines at a rate of 4.1 percent, while those that had reached the blastocyst stage by that point yielded stem cell lines with an 8.5 percent success rate.

The authors point out that these efficiency rates are similar to that of normal frozen embryos.

“Prior work had suggested that poor qual-ity embryos would only rarely yield stem cell lines, but we have shown that blastocyst stage embryos are a robust source of stem cells,” said George Daley, who is also an associate professor of Biological Chemistry and Molecular Pharma-cology at Harvard Medical School.

The research was funded through a private philanthropic donation from Joshua and Anita Bekenstein, as well as through support from the Burroughs Wellcome Fund and the Harvard Stem Cell Institute.

Contact: Paul Lerou, M.D., [email protected]

Contact: George Daley, M.D., Ph.D., 617-919-2013

-=0=- Stroke Victims May Benefit From Stem Stroke Victims May Benefit From Stem Cell TransplantsCell Transplants

S troke victims may benefit from human mes-enchymal stem cell (hMSC) or bone marrow

stromal cell (BMSCs) transplantation, according to two studies published in the current issue of Cell Transplantation (Vol.16 No.10).

In both studies, the migration of chemi-cally “tagged” transplanted stem cells were tracked to determine the degree to which the


transplanted cells reached damaged areas of the brain and became therapeutically active.

In a study carried out by Korean research-ers, labeled hMSCs (early precursor cells to mus-culoskeletal, blood, vascular and urogenital sys-tems) were transplanted into animal stroke mod-els with cerebral artery occlusion and tracked by magnetic resonance imaging (MRI) at two days, one week, two weeks, six weeks and ten weeks after transplant.

“Cells started showing indications of mi-gration as early as one or two weeks following transplantation,” said lead author Jihwan, Song, D.Phil., of the Pochon CHA University College of Medicine. “At 10 weeks, the majority of the cells were detected in the core of the infarcted area.”

The study concluded that there is a strong tendency for transplanted hMSCs to migrate to-ward the infarcted area regardless of injection site but that the degree of migration was likely based on differences in each animal’s ischemic condi-tion.

“We speculate that the extensive migra-tory nature of stem cells and their utilization will provide an important tool for developing novel stroke therapies,” said Song.

In a joint Canadian, Chinese study, BMSCs or connective tissue cells were injected into animals 24 hours following middle cerebral artery occlusion.

Using laser scanning confocal microscopy to track fluorescent signals and immuno markers attached to the cells, researchers found that within seven days of the injection the BMSCs had mi-grated through the region of the middle cerebral artery into the scar area and border zone of the ischemic region.

“We evaluated vascular density in the ischemic region in all animals seven days after cell transplantation,” said study lead author Ren-Ke Li, M.D., Ph.D. “The animals exhibited sig-nificant reductions in scar size and cell death and improvements in neurological function when compared to controls that received no BMSCs.”

Researchers concluded that the intrave-nous delivery of bone marrow-derived cells may enhance tissue repair and, in turn, functional re-


26


covery after a stroke. While the potential mechanisms for this

recovery are unclear, among the possibilities are that the brain microenvironment early on follow-ing a stroke may mimic brain development.

Subsequent elevated levels of growth fac-tors might enhance homing of BMSCs to the in-jured area and induce cell proliferation.

“Our results support the potential thera-peutic use of BMSCs after a stroke,” said Li.

“Both studies lend important support to a growing body of laboratory evidence that bone marrow is a remarkable adult stem cell source for transplant therapy following stroke,” said Cell Transplantation associate editor Cesar V. Borlon-gan, Ph.D. of the Medical College of Georgia. “The non-invasive MRI visualization of pre-labeled BMSCs could become a routine clinical marker for transplanted cells as well as for safety and efficacy.”

Contact: Jihwan Song, 82-234-683-393, [email protected]

-=0=- Chinese Hospital Claims Batten Chinese Hospital Claims Batten Disease Breakthrough Disease Breakthrough

A Chinese hospital said on January 30 that it has successfully used stem cells to improve

and potentially prolong the life of six-year-old American boy suffering from Batten disease.

The hospital said that after undergoing the comprehensive stem cell therapy program at Tiantan Puhua Hospital Stem Cells Center (Beijing, China), the child’s family reported “a significant reversal in the recent swift deteriora-tion of [his] motor skills, giving real hope that he will live long enough for a scientific cure to be found.”

Since returning to California, the boy’s hands are unclenched and are no longer spastic.

The family reported reversal of other symptoms as well.

Batten disease, also known as Spielmeyer-Vogt-Sjogren-Batten Disease, is the most com-mon form of a group of disorders called neuronal



ceroid lipofuscinoses, or NCLs. Due to a genetic defect at birth, over time

those with NCL suffer progressive nervous sys-tem breakdown leading to mental impairment, worsening seizures, increasing loss of sight and motor skills until shortly before death they be-come blind, bedridden, suffer dementia, and are incommunicable.

Tiantan (Temple of Heaven) Puhua Neu-rosurgical Hospital, a hospital under TP Biomedi-cal Ltd., is a world-class neurological treatment facility in Beijing that collaborates with the Stem Cells Research Center of Peking University, a stem cells research center.

Contact: http://www.stemcellspuhua.com

-=0=- Indian Center To Use Stem Cells To Indian Center To Use Stem Cells To Fight BlindnessFight Blindness

T he Champalimaud Foundation (Hyderabad, India) said on January 29 it has launched the

Champalimaud Center of Translational Eye Re-search (C-TRACER) to use stem cell science de-veloped at the LV Prasad Eye Institute, a transla-tional vision research center, in the treatment of blindness.

The technique enables eye doctors to take cells from living adults and use them to grow the outer part of corneas.

In one of the most revolutionary proce-dures in medical science today, doctors at the In-stitute have also begun using stem cells from the lip to produce corneas for implantation into the blind patient to restore sight.

C-TRACER will focus on the following areas: research and therapy through the utilization of stem cells in vision-related illnesses; transla-tional research utilizing existing and novel clini-cal methodologies, with the objective of further-ing the knowledge of vision in such a way that it can be readily applied to the patient; exchange programs involving scientists; and introduction of “capacity building” programs in developing coun-tries.

The Champalimaud Foundation is com-


27


mitted to supporting cutting-edge developments in medical science in the fields of vision, neuro-science, and oncology.

Contact: http://www.fchampalimaud.org

-=0=- Stem Cell Society Responds to Stem Cell Society Responds to Initiatives in President’s AddressInitiatives in President’s Address

I n response to Pres. Bush’s State of the Union Address, the International Society for Stem

Cell Research said it applauded the President’s direction to federal agencies to provide additional funding for induced pluripotent stem cell (iPS cells) research, but stressed that this action is not sufficient to allow all important stem cell research to be done.

Bush acknowledged in his address on January 28 the landmark achievement of stem cell scientists who have demonstrated for the first time that human skin cells can be converted into induced pluripotent stem cells (iPS cells), which behave like embryonic stem cells.

“Although exciting, iPS cell research does not eliminate the need to pursue the great promise of human embryonic stem cell research, and we reiterate our call for the expansion of Federal funding for research for embryonic stem cell lines derived after August 9, 2001,” the organization said in a statement. “The technology used to gen-erate iPS cells holds great promise for creating patient- and disease-specific cell lines for re-search purposes. However, a great deal of work remains before these methods can be used to gen-erate stem cells suitable for safe and effective therapies.”

ISSCR said “scientists do not know how to produce iPS cells without introducing multiple viruses into the cells, which may cause extensive genome disruption and has been linked to cancer causation in animal models.”

Contact: http://www.isscr.org

-=0=-



Human Stem Cells Aid Stroke Recovery Human Stem Cells Aid Stroke Recovery In RatsIn Rats

N eural cells derived from human embryonic stem cells helped repair stroke-related dam-

age in the brains of rats and led to improvements in their physical abilities, according to a new study by researchers at the Stanford University School of Medicine.

The study, to be published in the February 20 issue of the journal PLoS ONE, marks the first time researchers have used human embryonic stem cells to generate neural cells that grow well in the lab, improve a rat’s physical abilities and consistently don’t form tumors when trans-planted.

Though the authors caution that the study is small and that more work is needed to deter-mine whether a similar approach would work in humans, they said they believe it shows the poten-tial for using stem cell therapies in treating strokes.

Senior author Gary Steinberg, M.D., Ph.D., a Stanford neurosurgery professor, said the disease creates a massive burden for the 750,000 people who suffer strokes in the United States each year, along with their families and the medical system.

“Human embryonic stem cell-based thera-pies have the potential to help treat this complex disease,” Steinberg said.

He said he hopes the cells from this study can be used in human stroke trials within five years.

Human embryonic stem cells are able to form any cell type in the body.

Pushing those cells to form neurons rather than other types of cells has been a substantial hurdle, as has avoiding the cells’ tendency to form tumors when transplanted.

Because embryonic stem cells are still im-mature and retain the ability to renew themselves and produce all tissue types, they tend to grow uncontrollably into tumors consisting of a mass of different cells.

First author Marcel Daadi, Ph.D., a senior scientist in Steinberg’s lab, said the team over-


28


came both obstacles by growing the embryonic stem cells in a combination of growth factors that nudged the cells to mature into stable neural stem cells.

After six months in a lab dish, those neu-ral stem cells continued to form only the three families of neural cells (i.e., neurons, astrocytes and oligodendrocytes) and no tumors.

Convinced that the cells appeared safe, Daadi and co-author Anne-Lise Maag, a former Stanford medical student, transplanted those cells into the brains of ten rats with an induced form of stroke.

At the end of two months, the cells had migrated to the damaged brain region and incor-porated into the surrounding tissue.

None of the transplanted cells formed tu-mors.

Once in place, the replacement cells helped repair damage from the induced stroke.

The researchers mimicked a stroke in a re-gion of the brain that left one forelimb weak.

This model parallels the kinds of difficul-ties people experience after a stroke.

Testing at four weeks and again at eight weeks after the stem cell transplants showed the animals were able to use their forelimbs more normally than rats with similarly damaged brain regions that had not received the transplants.

“The great thing about these cells is that they are in unlimited supply and are very versa-tile,” Daadi said.

The neural cells the group generated grew indefinitely in the lab and could be an ongoing source of cells for treating stroke or other injuries, he said.

In previous studies, Steinberg and others have implanted cells from cord blood, bone mar-row, fetal and adult brain tissue or derived from mouse embryonic stem cells into stroke-damaged rats, but none of those cell types appear as prom-ising as the cells in this study, the researchers said.

Those cells are not as easy to produce in large scale for the appropriate quality assurance program to meet a sufficient patient population for multi-center clinical trials.

Before researchers can begin testing these



neural cells in human stroke patients, Steinberg and Daadi said, they need to verify that the cells are effective in other animal stroke models and don’t form tumors.

They are working with industry groups to grow the cells in accordance with U.S. Food and Drug Administration guidelines, which would be necessary before they could move on to human trials.

The work was funded by the National In-stitutes of Health; Russell and Elizabeth Siegel-man; Bernard and Ronni Lacroute; the William Randolph Hearst Foundation; the Edward E. Hills Fund; and Gerald and Marjorie Burnett.

Citation: Daadi MM, Maag A-L, Steinberg GK (2008), “Adherent Self-Renewable Human Embryonic Stem Cell-Derived Neural Stem Cell Line: Functional Engraftment in Ex-perimental Stroke Model;” PLoS ONE 3(2): e1644. doi:10.1371/journal.pone.0001644

Contact: http://www.plosone.org/doi/pone.0001644 Contact: Gary Steinberg, 415-723 5575

-=0=-

Human Skin Cells Reprogrammed Into Human Skin Cells Reprogrammed Into Embryonic Stem CellsEmbryonic Stem Cells

C onfirming the work reported earlier by Japa-nese and American researchers, stem cell

scientists at the University of California, Los An-geles, have reprogrammed human skin cells into cells with the same unlimited properties as em-bryonic stem cells without using embryos or eggs.

Led by scientists Kathrin Plath and Wil-liam Lowry, UCLA researchers used genetic al-teration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, which have the abil-ity to become every cell type found in the human body.

Four regulator genes were used to create the cells, called induced pluripotent stem cells or iPS cells.

The UCLA study confirms the work first reported in late November of researcher Shinya


29


Yamanaka at Kyoto University and James Thompson at the University of Wisconsin.

The UCLA research appears Feb. 11, 2008, in an early online edition of the journal Proceedings of the National Academy of the Sci-ences.

The implications for disease treatment could be significant.

Reprogramming adult stem cells into em-bryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine.

A patient’s skin cells, for example, could be reprogrammed into embryonic stem cells.

Those embryonic stem cells could then be prodded into becoming various cells types, in-cluding beta islet cells to treat diabetes, hemato-poetic cells to create a new blood supply for a leukemia patient, motor neuron cells to treat Park-inson’s disease.

“Our reprogrammed human skin cells were virtually indistinguishable from human em-bryonic stem cells,” said Plath, an assistant pro-fessor of biological chemistry, a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and lead author of the study. “Our findings are an important step towards manipulating differentiated human cells to generate an unlimited supply of patient specific pluripotent stem cells. We are very excited about the potential implications.”

The UCLA work was completed at about the same time the Yamanaka and Thomson re-ports were published.

Taken together, the studies demonstrate that human iPS cells can be easily created by dif-ferent laboratories and are likely to mark a mile-stone in stem cell-based regenerative medicine, Plath said. These new techniques to develop stem cells could potentially replace a controversial method used to reprogram cells, somatic cell nu-clear transfer (SCNT), sometimes referred to as therapeutic cloning.

To date, therapeutic cloning has not been successful in humans.

However, top stem cell scientists world-wide stress that further research comparing these



reprogrammed cells with stem cells derived from embryos, considered the gold standard, is neces-sary.

Additionally, many technical problems, such as the use of viruses to deliver the four genes for reprogramming, need to be overcome to pro-duce safe iPS cells that can be used in the clinic.

“Reprogramming normal human cells into cells with identical properties to those in embry-onic stem cells without SCNT may have impor-tant therapeutic ramifications and provide us with another valuable method to develop human stem cell lines,” said Lowry, an assistant professor of molecular, cell and developmental biology, a Broad Stem Cell Center researcher and first au-thor of the study. “It is important to remember that our research does not eliminate the need for embryo-based human embryonic stem cell re-search, but rather provides another avenue of worthwhile investigation.”

The combination of four genes used to re-program the skin cells regulate expression of downstream genes and either activate or silence their expression.

The reprogrammed cells were not just functionally identical to embryonic stem cells.

They also had identical biological struc-ture, expressed the same genes and could be coaxed into giving rise to the same cell types as human embryonic stem cells.

The UCLA research team included four young scientists recruited to UCLA’s new stem cell center in the wake of the passage of Proposi-tion 71 in 2004, which created $3 billion in fund-ing for embryonic stem cell research.

The scientists were drawn to UCLA in part because of California’s stem cell research friendly atmosphere and the funding opportunities created by Proposition 71.

In addition to Plath and Lowry, the team included Amander Clarke, an assistant professor of molecular, cell and developmental biology, and April Pyle, an assistant professor of microbiol-ogy, immunology and molecular genetics.

The creation of the human iPS cells is an extension of Plath’s work on mouse stem cell re-programming.

Plath headed up one of three research (Continued on page 30)

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teams that were able to successfully reprogram mouse skin cells into mouse embryonic stem cells.

That work appeared in the June 2007 issue of Cell Stem Cell.

Contact: http://www.stemcell.ucla.edu

-=0=- Liver Stem Cell Discovery Offers New Liver Stem Cell Discovery Offers New Treatment PossibilityTreatment Possibility

R esearchers have discovered both normal and “cancer” stem cells in the liver and, by com-

paring their genetic “signatures,” have found evi-dence to suggest that a new type of experimental cancer drug might offer benefit in treating liver cancer.

Many scientists believe up to 40 percent of liver cancer is caused by master stem cells in the organ that have lost all growth control.

But, despite years spent looking, no one has ever found these liver “cancer” stem cells, or even normal stem cells in the organ.

But in the February 19 issue of the Pro-ceedings of the National Academy of Sciences (PNAS), researchers at Georgetown University Medical Center report the amazing discovery of such cells.

In fact, preliminary result from the current study indicate that use of a stat3 inhibitor dra-matically inhibited liver cancers in human cancer cell lines and mice.

“After locating the cancer stem cells that help control development of these tumors, we were able to find a potential vulnerability that might form the basis of a new treatment for this disease, which is greatly needed,” said the study’s lead author, Lopa Mishra, M.D., director of can-cer genetics in the department of surgery at Georgetown University.

Liver (hepatocellular) cancer is one of the most lethal and prevalent cancers in the world, and the number of cases diagnosed in the United States has risen sharply recently, Mishra said.

Five-year survival is less than five percent because the only treatment that has shown any



benefit is liver transplantation or surgery, but an operation to remove tumors is only possible when the cancer mass is very small.

Unfortunately, most cancers are diagnosed when tumors are much larger, she said.

The findings culminate decades of re-search in Mishra’s laboratory into the genetic pathways important to development of liver can-cer.

An early pivotal discovery was that the transforming growth factor beta (TGF-ß) pathway was crucial to the development of the cancer, be-cause when researchers eliminated the molecular pathway controlled by TGF-ß in mice, the ani-mals developed liver cancer.

The TGF-ß family of proteins helps keep stem cells in an undifferentiated state, but also, when appropriate, guide development of these cells into specialized cells.

They also are powerful suppressors of cancer development, she said.

Later work showed that loss of a gene known as ELF, which is common to stem cells and is found within the TGF-ß pathway, was suf-ficient to induce liver cancer to form.

It is now known that ELF is lost in more than 90 percent of human hepatocellular cancers.

While these studies suggested that stem cells gone wild were key to liver cancer develop-ment, no one could find such cancer stem cells, or any stem cells, - in liver tissue in order to test the theory.

Georgetown transplant surgeon Lynt Johnson, M.D., suggested looking for stem cells in donor liver tissue that had been newly trans-planted into patients with a failing organ.

Stem cells in this tissue would be particu-larly active, Johnson reasoned, because they would be busy creating new liver cells.

(The liver is the only human organ that is capable of large scale, natural regeneration.)

Biopsies taken from six surgery patients of liver tissue up to four months past transplanta-tion were studied.

In this regenerating tissue Mishra and her team finally found normal stem cells.

They were rare , only two to four cells per 30,000-50,000 cells, but they expressed all the


31


proteins known to be associated with stem cells, such as Stat3, Oct4, Nanog, ELF, and receptor for the TGF-ß protein.

“These cells were working really hard, ex-pressing all of these proteins in abundance,” Mishra said. “In our staining tests they looked like stars, surrounded by shells of cells that were also expressing TGF-ß in order to make new liver cells.”

To find cancer stem cells, the researchers examined tissue from 10 patients with liver can-cer using the same antibody test that located the stem cells in the regenerating livers.

“We found that all of these stem cells had lost TGF-ß,” she said. “Without the brakes that TGF-ß puts on cancer, the stem cells had turned into bad guys.”

The scientists turned to mouse models of liver cancer to see what would happen if they took out the “stemness” in the cancer stem cells and found that only 1 in 40 mice bred without a stat3 gene developed liver cancer. “But with the stat3 gene intact, 70 percent of mice developed the cancer,” Mishra said.

As a final step in the study, Georgetown oncologists are treating mice with liver cancer that had normal stat3 gene but are missing TGF-ß with an experimental stat3 inhibitor drug in devel-opment by the National Cancer Institute to shut down stat3.

Early studies using stat3 inhibitors in gas-trointestinal cancers indicate that the drug has lit-tle toxicity.

Contact: Lopa Mishra, 202-687-5707, [email protected]

-=0=- Progenitor Cell Transplantation Progenitor Cell Transplantation Benefits Acute Lung Injury Benefits Acute Lung Injury

T he use of a patient’s own progenitor cells may be effective in the treatment of acute

lung injury and acute respiratory distress syn-drome (ARDS), according to a new animal study.

The discovery, published in this month’s Anesthesiology, represents a milestone in acute



lung injury therapy because it is based on remov-ing and then reintroducing cells from the same in-dividual (i.e., autologous cells).

In contrast to stem cell transplantation, the new technique employs a subject’s own progeni-tor cells, which are present in adults and are more restricted than stem cells in the type of tissues they can subsequently form.

Chen-Fuh Lam, M.D., Ph.D., and col-leagues from the National Cheng Kung Univer-sity College of Medicine and Hospital in Taiwan, found convincing evidence that autologous trans-plantation of cells that eventually form blood ves-sel linings ― so-called endothelial progenitor cells (EPCs) ― had markedly positive effects on animals being treated for acute lung injury.

Several pharmacologic agents have been examined in the management of acute lung injury over the past decades, Lam said, but few of them have met with much success.

In Lam’s study, EPCs derived from circu-lating bone marrow were removed from a healthy animal and allowed to grow for one week in a laboratory culture.

The cells were then reintroduced into the circulatory system of the same animal that had undergone induced acute lung injury.

“Our results obtained from a rabbit model of acute lung injury showed that transplantation of these premature EPCs significantly improved the function of lung blood vessels, reduced the amount of water that leaked into lungs, and de-creased bleeding in the lungs,” he said

Lam and colleagues also performed addi-tional laboratory experiments on the antioxidant capacity of premature human EPCs compared to relatively more mature endothelial cells derived from human umbilical cords.

They found that certain helpful antioxi-dant effects were greater in the premature EPCs than in the more mature endothelial cells.

In a companion editorial, Ellen L. Burn-ham, M.D., of the University of Colorado Health Sciences Center, described the potential influ-ence of the study in this field of research.

“These findings suggest a potential mechanism whereby infusion of premature EPCs acts to normalize the oxidative environment of the


32


injured lung and potentially lay the groundwork for adequate lung repair and normalization of cel-lular function,” Burnham wrote.

Burnham and Lam emphasized that more animal studies need to be performed before EPC transplantation for acute lung injury can be con-sidered safe for human subjects.

Several animal studies have provided use-ful direction for further research, but animal re-search is considered basic science: findings do not always translate to the complex physiological sys-tem of human beings.

Contact: http://www.anesthesiology.org Contact: http://www.asahq.org Contact: http://www.ncku.edu.tw Contact: Ellen L. Burnham,

[email protected]

-=0=- UK Scientists Hope To Test Stem UK Scientists Hope To Test Stem CellCell--Based Bone Repair Among Based Bone Repair Among Humans In 2 Yrs.Humans In 2 Yrs.

S everal British organizations are funding a £1.4 million (US$718,000) project at the Uni-

versity of Edinburgh to further develop a revolu-tionary way to mend damaged bones and cartilage using a patient’s own stem cells.

The scientists hope to launch a clinical trial within two years.

The initiative, paid for by the UK Stem Cell Foundation, the Medical Research Council and Scottish Enterprise, and the Chief Scientist’s Office, could have a major impact on treating conditions such as osteoarthritis as well as trauma victims whose bones have been shattered beyond repair.

It involves using a “bioactive scaffold” made to protect the stem cells and simulate their growth into bone or cartilage once they are placed in the affected area.

The scaffold consists of a fairly rigid mesh structure, coated or impregnated with a drug that affects the patients cells.

“This is a novel approach in terms of treating damaged bones and cartilage,” said Dr.



Brendon Noble of the University of Edinburgh’s MRC Centre for Regenerative Medicine. “The aim is to translate the knowledge we have gained from bone biology studies into tangible treat-ments for patients.”

Researchers will also work with clini-cians, headed by Hamish Simpson, professor of orthopedics and trauma at the University of Edin-burgh, with a view to eventually translating their findings into treatments for patients.

As well as using cells derived from bone marrow, the scientists will work in collaboration with the Scottish National Blood Transfusion Ser-vice to culture bone forming cells derived from blood.

The advantage of these blood-sourced cells is that they can be extracted without the need for surgery.

The use of a patient’s own stem cells means that they are also unlikely to be rejected.

“In the UK, hip fractures kill 14,000 eld-erly people every year, more than many cancers. The worldwide market for orthopedic devices alone represents some $17 billion,” said Dr. Anna Krassowska, research manager for the UK Stem Cell Foundation. “This research has the potential not only to impact on a significant number of peo-ple’s lives but to open up one of the largest stem cell markets in the industry.”

For nearly a decade, scientists have known broadly the right chemical conditions required to encourage undifferentiated stem cells taken from a patient’s bone marrow to change into bone and cartilage cells in the laboratory.

However, the use of the “bioactive scaf-fold” being developed at the University of Edin-burgh aims to enable these cells to grow within the human body.

The initial clinical trial resulting from the laboratory work is likely to involve around 30 pa-tients, the researchers said.

The MRC Centre for Regenerative Medi-cine at the University of Edinburgh has one of the largest groups of stem cell researchers in Europe.

Scottish Enterprise, the main economic development agency for Scotland, has funded the project from its Stem Cell Translational Fund – a £5 million initiative provide co-funding to further


33


the clinical development of regenerative therapies using stem cell research

This is the UK Stem Cell Foundation’s first project in Scotland.

The Foundation supports advancing pio-neering stem cell research into medical practice.

The Chief Scientist Office (CSO) is the division of the Scottish Government Health Di-rectorate which supports and promotes high qual-ity research

Contact: http://www.ukscf.or Contact: http://www.scottish-enterprise.co Contact: http://www.scrm.ed.ac.uk Contact: http://www.show.scot.nhs.uk/cso

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Animal Safety Studies Set For Stem Animal Safety Studies Set For Stem Cell Therapy In Spinal Muscular Cell Therapy In Spinal Muscular AtrophyAtrophy

A collaborative effort among family mem-bers, a stem cell scientist, and a manufac-

turer of cells for use in research, said on February 19 it plans to push a potential stem cell therapy for spinal muscular atrophy (SMA) toward human clinical trials.

As a first step, the partnership is planning animal studies to be conducted in accordance with FDA regulations to assess the safety of motor neuron progenitors derived from human stem cells after transplantation.

Participating in the effort are Families of Spinal Muscular Atrophy (FSMA), a stem cell scientist at the University of California, Irvine (UCI), and a private firm called California Stem Cell, Inc. (CSC).

SMA is a genetic disorder that is the lead-ing genetic killer of children younger than two years of age.

SMA typically is marked by the degenera-tion of voluntary muscle movement, including the muscles that control crawling, walking, swal-lowing or breathing due to the dysfunction or death of motor neurons.

It is a debilitating and often fatal disease for which there is no treatment.



Safety studies are critical in advancing stem cell therapy into human trials for SMA.

High purity human motor neuron popula-tions for use in transplant therapies were devel-oped by CSC and have been used successfully in proof of concept efficacy and preliminary safety studies in the laboratory of Dr. Hans Keirstead at UCI with funding from FSMA.

CSC uses scalable manufacturing proto-cols to produce the large population of clinical-grade motor neuron progenitors required for the pivotal studies and future human clinical trials.

“This collaboration illustrates the breadth of skills that are required to take a potential treat-ment from the bench to the bedside,” said Keirstead. “I am confident that we have assem-bled the right team and the right plan to move this treatment forward with both diligence and speed.”

Studies are being conducted in parallel at both the Keirstead laboratory at UCI and the labo-ratory of Dr. Douglas Kerr at Johns Hopkins Uni-versity, with funding from FSMA, to show the benefit of human motor neuron progenitor re-placement in animal models of motor neuron dis-ease.

According to the partnership, stem cell therapy for SMA has the potential to replace the motor neurons lost during the disease course.

While other types of therapies have the potential to slow disease progression and possibly increase strength, motor neuron replacement through the use of stem cells is the only means to replace motor neurons once they are gone.

This strategy may be useful for treating multiple disorders such as spinal cord injury, transverse myelitis, and amyotrophic lateral scle-rosis (ALS) in addition to spinal muscular atro-phy.

Contact: http://www.curesma.org Contact: http://www.californiastemcell.com

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Damaged Hearts Treated With Muscle, Damaged Hearts Treated With Muscle, Fat And Bone Marrow Cells Fat And Bone Marrow Cells

C linical and pre-clinical studies using adult muscle stem cells derived from a patients

own thigh tissue to treat advanced heart failure were presented at a meeting focused on cell ther-apy for cardiovascular disease, sponsored by the Cardiovascular Research Foundation. Dr. Warren Sherman of Columbia Univer-sity and Dr. Nabil Dib of the University of Cali-fornia, San Diego presented data on a procedure involving delivery of cells via a thin plastic tube with an injection needle on the tip, inserted in the patients groin and directed to the inside of the heart in order to grow new muscle in the hearts scar tissue.

Sherman presented final one year results of the MYOHEART trial sponsored by Bioheart, Inc., in which 83 percent of patients treated in this manner with adult muscle stem cells, also known as myoblasts, improved.

Only 17 percent remained unchanged or worsened.

Eighty-three percent of myoblast treated heart failure patients improving compares favora-bly with the 369 patient “gold-standard” bi-ventricular pacer study where approximately 55 percent of the 187 treated patients showed im-provement in NYHA Class or quality of life score as compared to only 40 percent improvement for the 182 control patients who were on drug ther-apy alone, Sherman said.

A separate study led by Dib, sponsored by Advanced Cell Therapy, Inc., showed similar re-sults, and both groups have now moved onto Phase II/III placebo controlled trials currently in the process of enrolling together more than 495 patients.

The procedure (16 injections in a cardiac cath lab) takes about 45 minutes.

Dr. Keith March of the Indiana University Medical Center, Indiana Center for Vascular Biol-ogy and Medicine, Professor Patrick Serruys of the ThoraxCentre, Rotterdam, Netherlands, and Francisco Fernandez-Avils of Madrid, Spain all presented data related to the use of stem cells de-



rived from a patients own adipose (fat) tissue. Pre-clinical studies have demonstrated im-

proved blood flow and a reduction of scar size when adipose derived stem cells are provided within a short time period following the heart at-tack by coronary infusion.

March presented data that two cell types, adipose stem cells and endothelial progenitor cells, work in partnership to provide much more blood flow than either cell type can alone.

Clinical studies of cells from adipose tis-sue have begun at a number of centers worldwide.

We are very interested to see that cells from adipose tissue are being tested in these early trials, said March, noting that the use of one's own cells from fat tissue is potentially a very practical approach.

Various studies are being sponsored sepa-rately by Cytori Therapeutics, Inc., Tissue Gene-sis, Inc. and Bioheart, Inc.

Dr. Andreas M. Zeiher, M.D., of the Uni-versity of Frankfurt (Frankfurt, Germany), and a number of other researchers provided both pre-clinical and clinical data from the use of bone marrow derived cells.

These cells seem to function primarily by promoting growth of new blood vessels, which can help preserve tissue following a heart attack.

Data from clinical studies of hundreds of patients has demonstrated a noticeable improve-ment in heart function, especially in patients whose hearts start with low pumping ability.

More clinical studies are in progress. Sponsors of bone marrow cell studies in-

clude Osiris Therapeutics and Boston Scientific Guidant.

Dr. Marc Penn from Cleveland Clinic pre-sented pre-clinical data demonstrating that adult muscle stem cells (myoblasts) modified to over-express SDF-1 (stromalderived factor-1) are able to achieve significant improvements in the pump-ing ability of the heart.

Myoblasts alone in his study provided a 27 percent improvement of the pumping ability of the damaged animal hearts he treated, while SDF-1 modified myoblasts provided a 54 percent im-provement.

Penn is optimistic about the future of such (Continued on page 35)

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heart therapies. “Clearly this is a multi-year process,” he said. “We are only in Phase I, but the excitement over this treatment is a direct result of past successes.”

Contact: http://www.crf.org

-=0=- Blood Disorder Patients Improve With Blood Disorder Patients Improve With Own, Or Sibling’s, Cord Stem Cells Own, Or Sibling’s, Cord Stem Cells –– Study Study

A majority of blood disorder patients treated with stem cells from their own or a sibling’s

cord blood were cured or achieved disease remis-sion, according to a report presented at the Ameri-can Society for Blood and Marrow Treatment (ASBMT) annual meeting.

“This study provides important insights into the ability of transplant physicians to achieve successful outcomes using an individual’s own cord blood (autologous transplant) to treat an en-vironmentally-triggered blood disease or cord blood from a family member to treat certain ge-netic blood disorders and inherited bone marrow failure syndromes (IBMFs),” said Dr. Jennifer Willert, senior attending transplant physician and clinical professor at Rady Children’s Hospital, University of California - San Diego, and lead au-thor of this study. “In addition, this data suggests that the use of genetically-related cord blood may reduce the rate of mortality as well as the risk of treatment-related complications.”

The analysis examined transplant recipient data from 16 cases of nonmalignant blood disor-ders. Four of the patients were infused with their own cord blood stem cells to treat aplastic ane-mia, an acquired condition.

Twelve patients were transplanted with cord blood stem cells of a sibling for a range of inherited conditions including, thalassemia, sickle cell anemia, Fanconi anemia and Hurler syn-drome.

The review showed that two-thirds of the patients (10) were either cured or are in remis-sion, including half of the patients treated with their own cord blood.



Three patients died of complications unre-lated to their cord blood transplant; one patient experienced a relapse; and the outcomes status of two patients is not known.

All 16 cord blood collections were proc-essed and cryopreserved at Cord Blood Registry (CBR) and were viable for transplant when re-quested.

The average storage time prior to use was about 27 months; however, one child’s collection was stored for nine and half years and used to successfully cure that child’s aplastic anemia (autologous use).

According to previously published data, CBR said, transplantation of genetically-related umbilical cord blood has demonstrated clinical advantages over bone marrow, peripheral blood and unrelated umbilical cord blood.

Since cord blood stem cells are immu-nologically younger than other “adult” stem cell sources, they demonstrate more versatility and flexibility when used in transplantation.

Stem cell transplants from genetically-related sources (those from an immediate family member) result in better treatment outcomes than transplants from an unrelated donor and are asso-ciated with less frequent and less severe graft-vs.-host disease, a complication that occurs when the donor cells attack different parts of the body.

Cord blood is rapidly becoming a pre-ferred stem cell source in transplant therapy, with more than 10,000 cord blood transplants per-formed worldwide to-date.

“This study is relevant to any expectant parent considering whether or not to privately bank cord blood stem cells,” said Willert. “Individuals who have access to their own cord blood stem cells, as well as a sibling’s, have the best chance of treating a blood disorder that de-velops. For expectant parents who already have a family member with a diagnosed blood disorder that can be treated by cord blood stem cells, it’s important to know that there are free cord blood banking programs available - known as related donor or designated transplant programs - that provide immediate access to the genetically-related stem cells.”

Cord Blood Registry is a cord blood stem (Continued on page 36)

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cell processing and cryopreservation service that offers families access to genetically-related stem cells that are viable for medical use.

Contact: http://www.CordBlood.com

-=0=- Canadian Company Reports Favorable Canadian Company Reports Favorable Safety Results From Stroke Therapy Safety Results From Stroke Therapy TrialTrial

C algary, Alberta (Canada)-based Stem Cell Therapeutics Corp. (CA) on February 20 an-

nounced favorable results from a clinical trial testing the safety of the company’s stroke treat-ment.

The investigator-led Phase IIa open label safety trial (BETAS, or Beta-hCG + Erythropoi-etin in Acute Stroke) was conducted at the Uni-versity of California, Irvine, and Hoag Presbyte-rian Memorial Hospital (Newport Beach, Calif.)

The trial was the first test of the safety of NTx-265 in patients suffering acute ischemic stroke and to conduct a preliminary assessment of functional recovery in this patient population.

According to the company, results from the BETAS trial showed no serious adverse events related to NTx-265 in the 13 patients en-rolled.

Of these, eight patients completed the 90 day assessment term and each showed a clinically relevant improvement in their National Institutes of Health Stroke Scale (NIHSS) score of 4 points or greater, the company said.

Patients entered the trial with NIHSS scores ranging from 6-19 (moderate to severe).

In these patients, average baseline NIHSS was 8.3 plus/minus 4.1 (mean plus/minus SD) and improved in 8 of 8 patients to an average day 90 NIHSS of 2.5 plus/minus 1.8, an improvement in NIHSS score of 5.8 plus/minus 2.5 points.

Five of these eight patients had a day 90 Barthel Index score of 95-100 (out of 100); con-sistent with excellent outcome.

Specific assessments of neurological re-covery affected by NTx-265 were also favorable, including the Arm Motor Fugl-Meyer Scale, an



arm motor recovery assessment; Trailmaking A test, a measure of cognitive function; and meas-ures of neglect and aphasia.

Further, the drug regimen decreased the size of the infarct in 6 out of 8 patients overall, given a mean decrement in all eight of about 10 percent.

“The encouraging results from this trial are consistent with results previously reported as an interim analysis on April 10, 2007 and suggest great promise for our NTx-265 treatment for stroke, but interpretation of results from the BE-TAS trial is limited by small patient sample size and absence of a placebo control group,” said CEO Dr. Alan Moore. “Nevertheless, these re-sults represent an important first step in defining the safety of the NTx-265 regimen in patients with acute neurologic injury. Equally promising is early evidence in a small group of patients that consistent recovery of motor, cognitive and visual function may occur as a result of NTx-265 neuro-regenerative therapy for stroke.”

According to the company, the next devel-opment step for SCT is to build upon the promis-ing results from the BETAS clinical trial with the initiation of the REGENESIS proof of concept study.

REGENESIS is a Phase IIb prospective, randomized, double-blind, placebo controlled study of NTx-265: human Chorionic Gonadotro-pin (hCG) and epoetin alfa (EPO) in acute ischemic stroke patients.

The REGENESIS trial will be conducted at approximately 15-20 Canadian clinical trial centers and aims to enroll 134 patients in 2008.

The BETAS clinical data will be formally presented this week at the International Stroke Conference in New Orleans, La.

NTx-265 is a therapeutic regimen of two approved and clinically well-defined drugs, hu-man chorionic gonadotropin (hCG) and erythro-poietin (EPO), targeting the treatment of stroke.

The objective of the regimen is to stimu-late the growth and differentiation of new neurons to replace the brain cells that were lost or dam-aged by the stroke.

Animal studies have shown a significant recovery in motor function after receiving the


37


NTx-265 regimen 24-48 hours post stroke. Similar results have been found in SCT’s

Phase IIa BETAS safety trial, as announced on April 10, 2007. SCT has initiated a multi-centre, double-blind, placebo-controlled Phase IIb RE-GENESIS study for NTx-265 with primary end-points of efficacy.

Stem Cell Therapeutics is focused on the development and commercialization of drug-based therapies to treat central nervous system diseases.

Contact: http://www.stemcellthera.com

-=0=- Company Generates Functional Liver Company Generates Functional Liver Cells From Human Embryonic Stem Cells From Human Embryonic Stem CellsCells

W orcester, Mass.-based stem cell company Advanced Cell Technology, Inc. (ACTC)

said on February 21 that it has developed a robust and highly efficient process for the generation of high-purity hepatocytes (liver cells).

According to the company, the research described online in the journal Stem Cells is a big step toward the efficient generation of hepato-cytes for use in regenerative medicine and drug discovery.

The company said the research represents another effort to differentiate large numbers of human embryonic stem cells (hESCs) into critical replacement cell types.

In addition to demonstrating the efficient generation of hepatocytes, the company said it also has made significant progress in generating retinal pigmented epithelial (RPE) cells, heman-gioblasts to treat vascular disease, and red blood cells and platelets.

Two characteristics of embryonic stem cells, their versatility and capacity for unlimited self renewal, suggest the cells could serve as a po-tentially inexhaustible source of cells for replace-ment therapy.

As with other tissues, donor livers and hepatocytes are scare, a problem compounded by the low recovery and proliferative capacity of



adult hepatocytes. In addition to the cells’ potential use for

the treatment of liver disease, hESC-derived hepatocytes could also provide a valuable model for novel pharmaceutical drug discovery assays as well as new drug metabolism and cytotoxicity screens, particularly because the liver is a major site for detoxification.

“We have established a highly-efficient method for deriving hepatocytes from stem cells that mirrors events in embryonic development,” said company CSO Robert Lanza, M.D., senior author of the study. “Large scale production of hepatocytes using this method should greatly bol-ster their applications in basic research, clinical medicine and preclinical drug discovery.”

The method reported yielded synchronous populations of hepatocytes that were generated in clinically preferred conditions with minimum use of serum and cell feeders.

Highly enriched populations of definitive endoderm (DE) were generated from hESCs and then induced to differentiate along the hepatic lineage by the sequential addition of inducing fac-tors implicated in physiological hepatogenesis.

The differentiation process was largely uniform with cell cultures progressively express-ing increasing numbers of hepatic lineage mark-ers.

The hepatocytes exhibited functional he-patic characteristics such as glycogen storage, in-docyanine green uptake and release, and albumin secretion.

In an animal model of acute liver injury, the hESC-DE cells differentiated into hepatocytes and successfully repopulated the damaged liver.

Other authors on the paper were first au-thor Dr. Sadhana Agawal and Katherine Holton, a senior research associate at the company.

Contact: http://www.advancedcell.com

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Novocell Uses Stem Cells To Generate Novocell Uses Stem Cells To Generate Insulin In MiceInsulin In Mice

S an Diego, Calif.-based stem cell company Novocell, Inc., said on February 20 that its

scientists have demonstrated for the first time that human embryonic stem (hES) cells can be turned into pancreatic cells capable of producing insulin in mice.

The findings, reported in an online article on February 20, will be published in the journal Nature Biotechnology.

Type 1, or insulin-dependent diabetes oc-curs when the pancreas ceases to produce insulin due to an autoimmune response that causes the selective destruction of insulin producing cells.

People with Type 1 diabetes must take daily insulin and are candidates for pancreatic is-let cell transplantation, which provides the poten-tial to treat the disease.

The disease is most common in children and young adults, accounting for approximately 10 percent of diabetes cases.

The new research provides evidence sup-porting the potential future use of hES cells to re-place insulin-producing pancreatic cells that are destroyed in people with Type 1 diabetes, requir-ing them to receive regular insulin treatment, the company said.

The findings build on two previously re-ported studies by Novocell (Nature Biotechnology 2005 and 2006), in which Novocell scientists demonstrated a process that successfully engi-neers hES cells into specific cells necessary for pancreas formation, and endocrine cells capable of producing insulin and other pancreatic hor-mones.

In the new work, Novocell has demon-strated that implantation of hES-derived pancre-atic cells into mice results in the generation of glucose-responsive insulin producing cells.

The cells exhibit properties characteristic of functional adult pancreatic insulin producing cells in the pancreas.

The hES-derived cells provide protection in an animal model of diabetes characterized by loss of pancreatic insulin producing cells.



“Our data provide the first compelling evi-dence that hES cells can serve as a renewable source of functional insulin producing cells for diabetes cell replacement therapies,” said com-pany CSO Emmanuel Baetge, Ph.D., senior au-thor of the publication. “It also provides strong evidence that hES cell-derived endoderm cells are able to generate glucose-responsive insulin secret-ing cells that are functionally similar to adult hu-man beta cells.”

Current cellular therapy for diabetes is performed by transplanting donor-derived human islets combined with chronic immunosuppression.

While this has been demonstrated to be an effective therapy, the limited availability of do-nated pancreatic islets and the adverse side effects of long-term immunosuppression make this re-placement therapy unsuitable for the general dia-betes population.

Together with its stem cell engineering technology for insulin-producing cells, Novocell said it has also developed a delivery process by which such cells might be delivered to patients without the need for chronic immunosuppression.

The company’s encapsulation technology provides a protective, coating for cells, thus al-lowing them to be more readily accepted in the body without the chronic use of immunosuppres-sive drugs.

This encapsulation technology has been successfully tested in human clinical trials using human islets isolated from donor organs.

“By developing proprietary processes to successfully generate insulin-producing cells from hES cells in vivo and protecting these cells from immune system rejection, we have created a potential treatment option that could lead to the first widespread application of cell replacement therapy for the treatment of diabetes,” said CEO Alan J. Lewis, Ph.D.. “We look forward to the continued advancement of these technologies that hold such promise for transforming the treatment of diabetes.”

The Juvenile Diabetes Research Founda-tion estimates that more than 1.1 million people suffer from Type 1 diabetes in the United States alone.

About 30 percent of people with Type 2 (Continued on page 40)

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Novocell, with research operations in San Diego, California and Athens, Georgia, is dedi-cated to creating cell and drug therapies for diabe-tes and other chronic diseases.

Contact: http://www.novocell.com

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