4. Stem Cell Research

8/10/2019 4. Stem Cell Research

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This same reasoning is also applied to embryos and thefact they will exercise these capacities when theyeventually become fully developed humans.

Three types of concern have been expressed about thisargument:

the probability of IVF embryos developing into full-term successful births is low. The probability of an IVF embryo becoming a

successful birth depends heavily on human action andintervention , as well as other biological conditions

Some would argue, that it is not clear why somethingthat could become a person should be morally regardedas if it actually were a person.

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Embryos have Status as Divine

Creations For theistic ones, embryos warrant special

moral importance because they are divinecreations in being the beginnings of humanlife.

In other words, embryos are not ours todestroy (nor create).

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Embryos are Harmed by their

Destruction

loss of life ... is a harm that can be

inflicted on any organism; plants and non-human animals. Human organisms of everystage of development including the

embryonic can all suffer loss of life.

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Embryos have Status as Human

Life with Intrinsic Value A single human life has value no matter in what form

or shape

because of the complex creative investment it represents because of our wonder at the divine or evolutionary

processes that produce new lives from old ones, through which a human being will continue hundreds of

generations of cultures and forms of life and value

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Embryos have Status as Human

Life with Intrinsic Value Finally, when mental life has begun and flourishes, at the

process of internal personal creation and judgment bywhich a person will make and remake himself, it will bethe most powerful and inevitable source of empathy andcommunion we have with every other creature.

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Embryos have the Status

of Mere Body Parts Some might hold that embryos are merely parts of other

people's bodies until they reach a certain autonomous or

independent developmental stage.

Accordingly, embryos have no independent moral status atall, and are merely the property of the people from whose

body they came. The only respect due to embryos is therespect that should be accorded other people's property.

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Novel methods Extraction of single blastomere without damaging

embryo and developed into independent hESClines

Chung et al ,Nature 2006; 439:216-19

Altered Nuclear Technique (ANT)

genetically modifying the somatic nucleus so thatinduced pluripotent stem cells are produced

meissener & Jaenisch Nature 2006;439:212-15


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First clinical trial using hESC

GERON Co, 2005-2006

Aldhous, Nature 2005;434:94-6


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Existing lines of hESC

414 lines are available in 20 countries

Characterization of these lines is limited- only 49% of lines are published in peerreviewed journals

Guhr et al Stem cells 2006;24:2187-91


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Maintenance of hESC

Immortal cells in undifferentiated state

Optimal growth conditions for future therapeuticapplications

Majority of hESC have been isolated andmaintained in fetal calf serum and mouseembryonic fibroblasts as feeder cell layers(Xenoproteins and xenosupports)


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Problems Transmission of interspecies virus transfer

Incorporation of foreign sugar molecule tohESC leading to immune response

It may also lead to impairment of cell

function & tissue development

Varki Am J Phys Anthropol Suppl 2001


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Research focus is on.

Use of human components instead of animalsources to avoid zoonosis

Fetal, adult muscle tissue, skin, Fallopian tube,endometrium, foreskin cells

Successful undifferentiated growth of hESC using

xenobiotic free feeder system

Richards ,Stem cells 2003;21:546-56


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Differentiation

Direct hESC to differentiate into specific cell lines

- drug development

- cell replacement therapeutics

Specific germ cell layers can be directed byadding specific growth factors


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Scientific Stem Cell Challenges

Stem cells represents a very small fraction of cells intissue. Isolate a small number of stem cells (finding a needle in a

haystack). Expand the number of stem cells for research and clinical

applications. Maintain genetic stability in culture and in recipient. Culture media has to be free of animal protein. Deliver cells to tissue of interest. Stem cells have to be functional. Avoid or restrict tissue rejection.


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Challenges to Stem Cell/Cloning

Research differentiation to the

appropriate cell

type(s) before usingclinically.

Recently, chromosomeabnormalities in threehuman ESC lines.


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Challenges to Stem Cell/Cloning

Research Stem cell development

or proliferation must be controlled once placed into patients.

Possibility of rejectionof stem cell transplants

as foreign tissues isvery high.


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Beware

Private companies promising wonders with stemcells - mostly in countries with unregulated laws

Ilic D, Regenerative med 2006;1:1-4

UKRAINE capital of ESC ?

but the references they quote do not haveinternational authenticity in peer reviewed

journals


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Stem Cell Research Legislation Governments around the globe have passed legislation to

regulate stem cell research. In the United States, laws prohibit the creation of embryos for research purposes.Scientists instead receive "leftover" embryos from fertilityclinics with consent from donors. Most people agree thatthese guidelines are appropriate.

Disagreements surface, however, when political partiesdebate about how to fund stem cell research. The federalgovernment allocates billions of dollars each year to

biomedical research. Legislators have had the uniquechallenge of encouraging advances in science andmedicine while preserving a respect for life.

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Stem Cell Research Legislation

U.S. President Bush, for example, limited federal fundingto a study of 70 or so hES cell lines back in 2001. Whilethis did slow the destruction of human embryos, many

believe the restrictions set back the progress of stem cellresearch.

President Obama overturned Bush's stem cell policy in

2009 to expand the number of stem cell lines available toresearchers.

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2009 GUIDELINES ON HUMAN STEM CELL RESEARCH


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National Institutes of Health Guidelines onHuman Stem Cell Research

On March 9, 2009, President Barack H. Obama issuedExecutive Order 13505: Removing Barriers to ResponsibleScientific Research Involving Human Stem Cells. TheExecutive Order states that the Secretary of Health andHuman Services, through the Director of NIH, maysupport and conduct responsible, scientifically worthyhuman stem cell research, including human embryonicstem cell (hESC) research, to the extent permitted by law.

This helps ensure that NIH-funded research in this area isethically responsible, scientifically worthy, and conductedin accordance with applicable law.

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2009 GUIDELINES ON HUMAN STEM CELL


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2009 GUIDELINES ON HUMAN STEM CELLRESEARCH

National Institutes of Health Guidelines on

Human Stem Cell Research

These guidelines are based on the following principles: Responsible research with hESCs has the potential to

improve our understanding of human health and illnessand discover new ways to prevent and/or treat illness.

Individuals donating embryos for research purposes

should do so freely, with voluntary and informedconsent.

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The Stem Cell Debate: Is it over? New breakthroughs may soon

bring this debate to an end.Scientists have larned how tostimulate a patient's own cells to

behave like embryonic stem cells.These so-called induced

pluripotent stem (iPS) cells arereducing the need for human

embryos in research and openingup exciting new possibilities forstem cell therapies.

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THE STORY OF IPS CELLS

In 2007, scientists were able to turn adifferentiated cell back into a stem cellwith the potential to become any type ofcell in the body.

The difference between a stem cell and adifferentiated cell is reflected in the cells'DNA. In a stem cell, the DNA is arrangedloosely, with its genes ready to springinto action. As signals enter the cell and

differentiation begins, genes that will not be needed are shut down, and genes thatwill be required for a specialized functionremain open and active.

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By introducing a cocktail of 24 different genes, thescientists were able to convert differentiated cells into stemcells. They gradually eliminated genes from the mixture,and in the end they were able to turn differentiated cellsinto stem cells by activating just 4 genes. These genesappear to be remodeling the cells' DNA, unlocking thegenes that were shut down during differentiation.

Armed with the ability to reverse the differentiation process, scientist are exploring new ways to use stem cellsin research and medicine.

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d d l i S C ll


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Induced Pluripotent Stem Cells

Induced pluripotent stem cells(iPSCs) are adult cells that have been genetically reprogrammedto an embryonic stem cell likestate by being forced to expressgenes and factors important formaintaining the defining

properties of embryonic stemcells

Human iPSCs also express stemcell markers and are capable ofgenerating cells characteristic ofall three germ layers.

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With iPS cells now available

as an alternative to hES cells,the debate over stem cellresearch is becomingincreasingly irrelevant. Butethical questions regardinghES cells may not entirely goaway.

Inevitably, some humanembryos will still be needed

for research. iPS cells are notexactly the same as hES cells,and hES cells still provide

important controls: they

are a gold standard againstwhich the "stemness" ofiPS cells is measured.

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Some experts believe it'swise to continue the studyof all stem cell types,

since we're not sure yetwhich one will be themost useful for cellreplacement therapies.

An additional ethicalconsideration is that iPScells have the potential to

develop into a humanembryo, in effect

producing a clone of thedonor. Many nations are

already prepared for this,having legislation in placethat bans human cloning

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GENE CLONING

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Cloning


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Cloning

Different processes for duplicating biologicalmaterial. Diff types = technologies can be used for other

purposes besides producing the genetic twin of

another organism. 1. Embryo cloning, 2. Reproductive cloning

3. Therapeutic cloning.

R bi t DNA T h l DNA


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Recombinant DNA Technology or DNACloning

1970s = common practice in MB labs

Recombinant DNA technology," "DNA cloning,""molecular cloning or "gene cloning

Transfer of a DNA fragment of interest from oneorganism to a self-replicating genetic elementeg. bacterial plasmid.

The DNA of interest can then be propagated ina foreign host cell.

Scientists studying a particular gene often usebacterial plasmids to generate multiple copies ofthe same gene.


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How?

DNA fragment containingthe gene of interest is cutfrom chromosomal DNAusing RE.

United with a plasmid that

has been cut with the sameRE. Fragment of chromosomal

DNA + cloning vector ="recombinant DNAmolecule."

The recombinant DNA canthen be reproduced alongwith the host cell DNA.


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Reproductive Cloning

Adult DNA cloning This technique which is intended to produce a duplicate of

an existing animal. It has been used to clone a sheep and other mammals. The DNA from an ovum is removed and replaced with the

DNA from a cell removed from an adult animal. Then, thefertilized ovum, now called a pre-embryo, is implanted in awomb and allowed to develop into a new animal.

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R d ti l i g


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Reproductive cloning

Technology used to generate an animal that has the samenuclear DNA as another currently or previously existinganimal.

Somatic cell nuclear transfer (SCNT), = transfer of GMfrom the nucleus of a donor adult cell to an egg whosenucleus, and GM has been removed.

The reconstructed egg containing the DNA from a donorcell must be treated with chemicals/ electric current tostimulate cell division.

Once the cloned embryo reaches a suitable stage, it istransferred to the uterus of a female host where it continuesto develop until birth .

S i C ll N l T f (SCNT)


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Somatic Cell Nuclear Transfer (SCNT) technique used in CLONING

May be ethically acceptable as you are not using embryos by conventional

methods


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Dolly the sheep

The first mammal to be clonedwas put down by lethal injectionFeb. 14, 2003.

Prior to her death, Dolly hadbeen suffering from lung cancerand arthritis.

Studies showed that telomeresare shortened, a phenomenonthat is associated with cellularaging


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Reproductive cloning

The possibility of human cloning, raised whenScottish scientists at Roslin Institute created Dolly(Nature 385, 810-13, 1997),

Since Dolly, sheep, goats, cows, mice, pigs, cats,and rabbits all using nuclear transfer technology. Attempts at cloning certain species such as

monkeys, chickens, horses, and dogs, have beenunsuccessful as some species

some may be more resistant to somatic cellnuclear transfer than others.

Process can be traumatic


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In 2001, scientists in Italy reported the successfulcloning of a healthy baby endangered wildsheep, now living in Sardinia.

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Problems of repro cloning Reproductive cloning is expensive and highly inefficient. > 90% of cloning attempts fail to produce viable offspring. > 100 nuclear transfer procedures could be required to

produce one viable clone.

Cloned animals tend to have compromised immunefunction and higher rates of infection, tumor growth, andother disorders.

Japanese studies have shown that cloned mice live inpoor health and die early.

1/3 calves born alive have died young, and many of them

were abnormally large. Dont live long enough to generate good data. In 2002, researchers at Cambridge reported that the genomes

of cloned mice are compromised = certain of genes functionabnormally.


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Human cloning:

the most controversial debate of the decade

Aroused worldwide interest and concern

because of its scientific and ethical implications

Is it morally acceptable?


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Questions to be raised

Is self-engineering acceptable? Will failures, eg. deformed offspring, be

acceptable? Will cloning lead to designer babies ? Who is socially responsible for cloned humans? Rights and legal protection?


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Opinions

95% public say no to cloning,but 95% of scientists say yes


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Reasons for cloning

Provide valuable research

Answer to infertility?


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Scenario 1

Scenario 1: A husband and wife whowish to have children but both are

carriers of a lethal recessive gene.

Rather than risk the one in four

chance of conceiving a child whowill suffer a short and painful

existence


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Scenario 2

Scenario 2 : Parents of a terminally illchild are told that only a BMT cansave the child's life:

With no donor available, parentsattempt to clone a human being

from cells of the dying child. Ifsuccessful, the new child could be a

match for BMT


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Concerns of human cloning

Act of human arrogance = Playing God Safety concerns = Due to the inefficiency

of animal cloning (1-2 viable offspring forevery 100 experiments) and the lack ofunderstanding about reproductivecloning = unethical to attempt to clone

humans. Technology only in animals, in men =

possibility of mutation/ bio damage?


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Individuality and Uniqueness = Fearthat a clone would not be anindividual but merely a carboncopy.

Would it have a soul? Clone would be constantly

compared = burdened withoppressive expectations .

Q t ti d ti l i g


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Quotations on reproductive cloning(creating duplicate humans):

Conservative position: "...scientists who envision medicalbreakthroughs using stem cells from human embryos arenow moving on to human cloning -- breeding people for

the purpose of harvesting their tissues and organs fromtheir bodies, then disposing of them. "

Liberal position: " Human cloning allows man to fashionhis own essential nature and turn chance into choice. Forcloning's advocates, this is an opportunity to remakemankind in an image of health, prosperity, and nobility; itis the ultimate expression of man's unlimited potential. "

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Quotations on therapeutic cloning (creating


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Quotations on therapeutic cloning (creatinghuman organs for transplanting):

Conservative position: "Cloning, even so-calledtherapeutic or experimental cloning, creates a new lifewithout a father, and reduces a mother to the provider of

an almost emptied egg. Nonetheless, it is a new human lifeand the determination to destroy it and limit its use to

scientific research for therapeutic ends compound furtherthe moral issues rather than protect mankind. As such,cloning embryonic human life under any circumstancecrosses an ethical line, takes an irrevocable step, fromwhich science can never turn back. " 3

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Quotations on therapeutic cloning (creating


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Quotations on therapeutic cloning (creatinghuman organs for transplanting):

Liberal position: "Therapeutic cloning will in time allow scientists to create organs that are a perfect match forthose in need of a transplant. The cloned organ would be

based on the recipients genetic material and would notrequire the use of debilitating immunosuppressivetherapies. There would also be no chance of rejection,which is fatal. Therapeutic cloning represents the ideal inorgan transplantation, as it would provide an unlimited

source of organs to anyone who needs them. The need forthese organs is dire ." 4

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R ligi Obj ti


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Religious Objections

The Roman Catholic Church, under the papacy of BenedictXVI, has condemned the practice of human cloning, in themagisterial instruction Dignitas Personae , stating that itrepresents a "grave offense to the dignity of that person aswell as to the fundamental equality of all people".

Sunni Muslims consider human cloning to be forbidden byIslam .The Islamic Fiqh Academy , in its Tenth Conference

proceedings, which was convened in Jeddah , Saudi Arabia in the period from June 28, 1997 to July 3, 1997, issued aFatw stating that human cloning is haraam (prohibited bythe faith).

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http://en.wikipedia.org/wiki/Sunni_Muslimshttp://en.wikipedia.org/wiki/Islamhttp://en.wikipedia.org/wiki/Islamic_Fiqh_Academyhttp://en.wikipedia.org/wiki/Jeddahhttp://en.wikipedia.org/wiki/Saudi_Arabiahttp://en.wikipedia.org/wiki/Fatw%C4%81http://en.wikipedia.org/wiki/Haraamhttp://en.wikipedia.org/wiki/Haraamhttp://en.wikipedia.org/wiki/Fatw%C4%81http://en.wikipedia.org/wiki/Saudi_Arabiahttp://en.wikipedia.org/wiki/Jeddahhttp://en.wikipedia.org/wiki/Islamic_Fiqh_Academyhttp://en.wikipedia.org/wiki/Islamhttp://en.wikipedia.org/wiki/Sunni_Muslims


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4. Stem Cell Research

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