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REGENERATION David A. Steenblock, M.S., D.O. Personalized Regenerative Medicine TM Mission Viejo, California 26381 Crown Valley Pkwy, St. 130, Mission Viejo, Calif, USA; 800-300-1063
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Regeneration with Dr. David Steenblock

Nov 13, 2014

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Dr. David Steenblock has been specializing in regenerative medicine for over 40 years. This power point discusses how stem cells can regenerate the body and help you heal. To learn more about stem cell treatments, call 1-800-300-1063.
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Page 1: Regeneration with Dr. David Steenblock

REGENERATION

David A. Steenblock, M.S., D.O.Personalized Regenerative Medicine TM

Mission Viejo, California

26381 Crown Valley Pkwy, St. 130, Mission Viejo, Calif, USA; 800-300-1063

Page 2: Regeneration with Dr. David Steenblock

REGENERATION

For optimum regeneration of a damaged organ or entire body, there are three important factors that need to be present.

Healthy Stem cells of a newborn Growth factors- levels of a newborn Thymus factors- levels of a newborn

Page 3: Regeneration with Dr. David Steenblock

What are Stem Cells?

Stem cells are the first cells of the embryo that build new life.

Stem cells continue to help with growth and tissue repair as we age, BUT slow down after 40 years of age.

Stem cells divide to create more stem cells so theoretically if all of your stem cells remain youthful, the body could repair itself forever and you would only die from accidents.

Page 4: Regeneration with Dr. David Steenblock

Hematopoietic Stem Cells

Hematopoietic stem cells (called CD34+) are multipotent, undifferentiated hematopoietic blood forming stem cells (RBC, WBC, Platelets).

Normal stem cells found in umbilical cord blood and bone marrow.

Form endothelial progenitors and endothelial cells of vessels.

CD34+ facilitates cell migration

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Hematopoietic Stem Cells

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Mesenchymal Stem Cells

Multipotent “structure forming” stromal stem cells.

They produce bone cells, skin, chondrocytes, fat cells, tendons, ligaments and muscle cells and the extracellular matrix that supports the neurons and other cells.

Most primitive are from Wharton’s jelly and umbilical cord blood.

Page 7: Regeneration with Dr. David Steenblock

Mesenchymal Stem Cells

More recently, they have been able to produce liver cells, pancreatic cells, heart cells, kidney cells and neuron-like cells.

They suppress immune function and are beneficial for auto-immune conditions

Fat is said to have 500 times more Mesenchymal cells per gram than unstimulated bone marrow has.

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Mesenchymal Stem Cells

Page 9: Regeneration with Dr. David Steenblock

Neural Stem Cells

Both the bone marrow of adults and the umbilical cord blood of newborn babies have very primitive cells that can easily divide into neurons and retinal (eye) cells.

This primitive subset of the hematopoietic stem cells has the CD34+CD 133+ (CD=Cluster of Differentiation molecule) on their surfaces.

Used for most stem cell treatments in a variety of conditions

Page 10: Regeneration with Dr. David Steenblock

Umbilical Cord Derived Stem Cells

Human umbilical cord derived stem cells include hematopoietic stem cells, mesenchymal stem cells, CD133+ neural progenitor cells, and Very Small Embryonic-like stem cells (VSELs). These cells are neuroprotective and can survive and often thrive in the ischemic brain.

Sun T and Ma QH. Repairing Neural Injuries Using Human Umbilical Cord Blood. Mol Neurobiol 2012: Dec 30. Epub ahead of print.

Page 11: Regeneration with Dr. David Steenblock

VSELs

Very small embryonic-like stem cells are the smallest (1-3 micron) and most primitive stem cells currently being studied and used in clinical human medicine around the world.

Work especially well in ALS CSF treatments and in severely damaged, ischemic tissue since they thrive in an ischemic environment.

Page 12: Regeneration with Dr. David Steenblock

Stem Cells

Stem cells are able to migrate, secrete trophic factors, promote neuroprotection and modulate the immune response.

Costa C, et al. Stem cell-based treatment of neurologic diseases. Med Clin (Barc) 2012; 139(5): 208-14.

Page 13: Regeneration with Dr. David Steenblock

Stem Cells

Stem cells create cell repair and replacement through the growth factors that they produce.

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Live Cell Therapy

Paul Niehans in 1931, believed that the patients improved with Live Cell therapy because:

1) cells injected into the muscles remain alive and migrate towards the organs that need them.

2) injected cells remain alive at the injection site for a prolonged period, being nourished there by the host’s circulation and activating the deficiencies of degenerated organs at a distance. ---(Growth Factors)

Page 15: Regeneration with Dr. David Steenblock

Stem Cells

Several studies have shown that the growth factors in stem cells are the healing factors. When the growth factors are removed by antibodies, there is little or no improvement in the animals.

Page 16: Regeneration with Dr. David Steenblock

The Dilemma of Stem Cells

Growth factors are very important. Growth of stem cells is what creates the

healing growth factors Death or inhibition of the stem cells will stop

the production of the growth factors Stem Cell treatments then fail!

Page 17: Regeneration with Dr. David Steenblock

Failure of Stem Cells

The raw material not healthy i.e. In bone marrow the patient must be

ambulatory for the bone marrow stem cells to be good.

Chronic hypoxia such as in severe COPD will make the bone marrow “sick” and poorly functional.

Page 18: Regeneration with Dr. David Steenblock

Failure of Bone Marrow tm

Acute or chronic infections. During traveling the person picks up a cold or

bacterial infection. Trauma to the head or other treated part will

disrupt growing blood vessels. Lack of growth hormones, thyroid, etc.

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Failure of Bone Marrow tm

Severe vibration from 3 days to 40 days after the transplant – as in prolonged driving over rough roads.

The vibration destroys the new blood vessels. Severe stress for whatever reason Toxins such as alcohol will kill newly forming

tissue.

Page 20: Regeneration with Dr. David Steenblock

Bone Marrow Transplants

Treat everyone as if they have just gotten pregnant and so need to follow the same guidelines.

For example, avoid all fish so as to avoid heavy metals.

Most patients with chronic disease should be properly treated for heavy metals, intestinal dysbiosis and infections before treatment.

Page 21: Regeneration with Dr. David Steenblock

Growth Factors

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Growth Factors

Adrenomedullin (AM) Angiopoietin (Ang) Bone morphogenetic proteins (BMPs) Brain-derived neurotrophic factor (BDNF) Cartilage-derived angiogenesis inhibitor Ciliary neurotrophic factor (CNTF)

Page 23: Regeneration with Dr. David Steenblock

Growth Factors

Epidermal growth factor (EGF) Erythropoietin (EPO) Fibroblast growth factor (acidic and basic

FGF) Glial-derived neurotrophic factor (GDNF) Granulocyte colony stimulating factor (G-

CSF)

Page 24: Regeneration with Dr. David Steenblock

Growth Factors

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

Hepatocyte growth factor (HGF) Insulin Insulin-like growth factor 1α and II (IGF) Interferons α,β, and γ (IFN)

Page 25: Regeneration with Dr. David Steenblock

Growth Factors

Interleukins Macrophage-activating factor (MAF) Macrophage colony-stimulating factor (M-

CSF) Melanocyte-stimulating hormone (MSH) Nerve growth factor (NGF) Neurotrophins 3 and 4 (NT-3 and NT-4)

Page 26: Regeneration with Dr. David Steenblock

Growth Factors

Placental growth factor (PIGF) Platelet-derived growth factor (PDGF) Transforming growth factor α and β (TGF) Thrombopoietin (TPO) Tumor necrosis factor α and β (TNF) Wnt Signaling Pathway Vascular endothelial Factor (VEGF)

Page 27: Regeneration with Dr. David Steenblock

Additional Growth Factors

Some of the best growth factors available for the clinicians of today include:

Cerebrolysin (extract of embryonic pig brain)

Thymus extracts Placenta extracts

Page 28: Regeneration with Dr. David Steenblock

Cerebrolysin

Cerebrolysin has neurotrophic factors and peptide fragments that reduce the effects of neurotoxicity.

Cerebrolysin attenuates blood-brain barrier disruption and brain damage from heat exposure.

Sharma HS, et al. Neuroprotective effects of cerebrolysin, a combination of different active fragments of neurotrophic factors and peptides on the whole body hyperthermia-induced neurotoxicity. Int Rev Neurobio 2012; 102: 249-76.

Page 29: Regeneration with Dr. David Steenblock

Cerebrolysin

Cerebrolysin decreases β-amyloid deposition and tau phosphorylation.

It also promotes neurogenesis in the dentate gyrus of the hippocampus.

In stroke studies, cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces apoptosis in ischemic lesions.

Page 30: Regeneration with Dr. David Steenblock

Cerebrolysin

Cerebrolysin promotes axonal regeneration, neuronal plasticity and neurogenesis in stroke, traumatic brain injury, Alzheimer’s and spinal cord injury.

Masliah E et al, The pharmacology of neurotrophic treatment with Cerebrolysin. Drugs Today 2012; 48 Suppl A: 3-24.

Page 31: Regeneration with Dr. David Steenblock

Cerebrolysin

The safety of Cerebrolysin from clinical trials and clinical use has shown that adverse reactions were generally mild and transient. Most adverse effects included vertigo, agitation, rash and feeling hot. The results in clinical trials showed the adverse events similar to the placebo-treated groups.

Thome J and Doppler E. Safety profile of Cerebrolysin. Drugs Today (Barc) 2012; 48 Suppl A:63-9

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Thymus Extract

The thymus plays a crucial role in generating T cells and maintaining homeostasis of the immune system.

With more than 30 peptides, they comprise an effective group of regulators, mediating important immune functions.

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Thymus Extract

Thymosin fraction 5 stimulates lymphocyte proliferation and differentiation.

Prothymosin α and thymosin α1 show promise in immunodeficiencies, autoimmune disease, and malignancies.

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Thymus Extract

Prothymosin α is able to trigger anticancer immune responses.

Ioannou K, et al. Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy. Cancer Immunol Immunother 2012; 61(5): 599-614.

Page 35: Regeneration with Dr. David Steenblock

Thymus Extract

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is expressed in epithelial cells at barrier surfaces. TSLP strongly activates dendritic cells but without producing proinflammatory cytokines interleukin12, 6, TNF and interleukin 1.

Hanabuchi S, et al. TSLP and Immune Homeostasis. Allergology International 2012; 61:19-25.

Page 36: Regeneration with Dr. David Steenblock

Thymus Degeneration

Serious involution occurs at 50 years of age. Associated with the development of

autoimmune diseases. Increased absorption of endotoxins from GI

tract. Results in increased inflammation of body,

osteoarthritis, RA, hypertension and other diseases of aging.

Page 37: Regeneration with Dr. David Steenblock

Thymus Regeneration

Supplements of equal parts of Arginine and lysine 3 grams of each per day,

Thymic epithelial progenitor cells, Mesenchymal stem cells, Immune stimulation-repetitive.

Page 38: Regeneration with Dr. David Steenblock

Thymus Regeneration

Interleukin 22 administration (mice), Thymus extracts from young animals, Growth Factors, cytokines, Androgen blockade in men (also increases

success rate of bone marrow stem cell transplantation).

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Placental Extract

Human placenta has been used for wounds, healing of burns, chronic ulcers and skin defects.

In this study with placental extracts, the mice showed an acceleration in the reduction of the wound size compared with the control group on the 3rd to 9th day.

Page 40: Regeneration with Dr. David Steenblock

Placental Extract

On the 6th day, there was a significant increase in transforming growth factor beta in the experimental group and on the 14th day, there was a statistically significant increase in VEGF in the experimental group.

The authors conclude that placental extract directly promotes wound healing.

Hong JW, et al. The effect of human placenta extract in a wound healing model. Ann Plast Surg 2010; 65(1): 96-100.

Page 41: Regeneration with Dr. David Steenblock

Placental Extract

In Korea, human placental extract is being used to treat various diseases, including chronic liver diseases, menopause syndrome, chronic fatigue, skin pigment diseases, etc. In this study menopausal women were given placental extract, resulting in reduced symptoms and reduced fatigue.

Kong MH, et al. Effect of human placental extract on menopausal symptoms. Menopause 2008; 15(2): 296-303.

Page 42: Regeneration with Dr. David Steenblock

The Nervous System

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The Nervous System

Neurotrophic growth factors promote proliferation in specific cells as well as regulate programmed cell death (apoptosis) in other cells.

Neurotrophins include nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, neurotrophin-3 and -4, and glial-derived neurotrophic factor.

Page 44: Regeneration with Dr. David Steenblock

Neural Growth Factor

Nerve Growth Factor

Page 45: Regeneration with Dr. David Steenblock

Neural Growth Factor (NGF)

Nerve growth factor is important for the growth, maintenance, and survival of certain neurons.

It functions as a signaling molecule. NGF is critical for the survival and maintenance

of sympathetic and sensory neurons. Without it, these neurons undergo apoptosis (programmed cell death).

Page 46: Regeneration with Dr. David Steenblock

Neural Growth Factor

Nerve growth factor promotes synaptic plasticity in cholinergic neurons.

It improves memory impairment. It also stimulates neurite outgrowth by

regulating cytoskeletal organization and cell adhesion.

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Brain-derived Neurotrophic Factor

Page 48: Regeneration with Dr. David Steenblock

Brain-derived Neurotrophic Factor

Brain-derived neurotrophic factor (BDNF) also supports neuronal survival.

It promotes neurogenesis and synaptic function.

BDNF also promotes long-term memory. BDNF is also expressed in the retina, motor

neurons, the CNS, the kidneys, prostate and pancreas.

Page 49: Regeneration with Dr. David Steenblock

Ciliary Neurotrophic Factor

Ciliary neurotrophic factor promotes neurotransmitter synthesis and neurite outgrowth. It also assists with neural and oligodendrocyte survival.

Page 50: Regeneration with Dr. David Steenblock

Neurotrophin-3

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Neurotrophin-3

NT-3 supports neuronal survival and differentiation.

It also promotes the growth and differentiation of new neurons and synapses.

Page 52: Regeneration with Dr. David Steenblock

Neurotrophin-4

NT-4/5 interacts with the low affinity NGF receptor and promotes neurite outgrowth.

Page 53: Regeneration with Dr. David Steenblock

Glial-derived Neurotrophic Factor

GDNF promotes the survival and differentiation of dopaminergic neurons and prevents apoptosis in motor neurons. It also assists with kidney development.

Page 54: Regeneration with Dr. David Steenblock

Glial-derived Neurotrophic Factor

GDNF creates a signaling complex with the receptor tyrosine kinase molecule RET which requires the presence of heparan sulfate glycoaminoglycans.

The GDNF family includes neurturin, artemin, and persephin.

GDNF shows promising results with Parkinson’s disease,ALS, alcohol and drug addiction.

Page 55: Regeneration with Dr. David Steenblock

Vascular Endothelial Growth Factor

Vascular endothelial growth factor is also important to neural function by

promoting the growth and repair of blood cells in the central and peripheral nervous system and

eliciting the assistance of BDNF and FGF in neurogenesis.

Page 56: Regeneration with Dr. David Steenblock

Stem Cells and the Brain

Mesenchymal stem cell transplants promote endogenous neuronal growth, reduce apoptosis and free radicals, promote synaptic connections from

damaged neurons, and reduce inflammation.

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Stem Cells and the Brain

Mesenchymal stem cells augment growth factor support to the brain by releasing

Brain-derived neurotrophic factor Glial-derived neurotrophic factor Nerve growth factor Fibroblast growth factor-2 Insulin growth factor-1 Vascular endothelial growth factor

Page 58: Regeneration with Dr. David Steenblock

Stem Cells and the Brain

Mesenchymal stem cell transplants also release:

Extracellular matrix molecules that support neural cell attachment, neural growth and axonal extensions.

Joyce N, et al. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med 2010; 5(6): 933-946.

Page 59: Regeneration with Dr. David Steenblock

Stem Cells and the Brain

Hematopoietic stem cells release VEGF for improving blood

circulation, Release GDNF to promote the growth of glial

cells and astrocytes to repair the white matter. Cerebral palsy responds well to white matter repair.

Page 60: Regeneration with Dr. David Steenblock

Stem Cells and the Brain

Hematopoietic stem cells also Release neurotrophin 3, nerve growth

factor, brain-derived neurotrophic factor and promote the growth of neural progenitor cells to stimulate the growth of a small percentage of neurons.

Bracci-Laudiero L et al. J Neuroimmunol 2003; 136(1-2): 130-9.

Chouthai NS et al. Prediatr Res 2003; 53(6): 965-9.

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Stroke and Growth Factors

Stem cell therapies can have little or no effect in those who drink alcohol or have infections or stress. Combining stem cell therapies with growth factors helps the patient get better results, whether or not the stem cells survive.

Page 62: Regeneration with Dr. David Steenblock

Stroke and Growth Factors

Cerebrolysin administration to 529 patients with a placebo group of 541 subjects showed better performance on the NIH Stroke Scale. In addition, the cerebrolysin group had a 10.5% mortality rate compared to a 20.2% rate with the placebo group.

Heiss WD, et al. Cerebrolysin in patients with acute ischemic stroke in Asia. Stroke 2012; 43(3): 630-6.

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The Heart

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Atrial Natriuretic Peptide

ANP is a powerful vasodilator and a polypeptide

hormone secreted by heart muscle cells. It maintains homeostasis in water,

sodium, potassium and fat. It is released in response to high blood

pressure.

Page 65: Regeneration with Dr. David Steenblock

Fibroblast Growth Factor

FGF is involved in angiogenesis, embryonic growth and wound healing.

It is involved in the proliferation and differentiation of various cells.

Heparan sulfate proteoglycans are required for FGF signal transduction.

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Hepatocyte Growth Factor

HGF regulates cell growth, and is important for embryonic development, adult regeneration and wound healing.

It is released by mesenchymal and hemato-poietic stem cells and acts on endothelial cells, epithelial cells and hematopoietic progenitor cells.

It activates a tyrosine kinase signaling cascade to promote the growth of new cells.

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Insulin-like Growth Factor

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Insulin-like Growth Factor

IGF is mainly secreted in the liver when stimulated by growth hormone.

It promotes cell proliferation and inhibits apoptosis (programmed cell death).

IGF 2 assists with fetal development and IGF1 assists with achieving our maximum growth and regulates neurogenesis. It is also involved in hearing.

Page 69: Regeneration with Dr. David Steenblock

Platelet-derived growth factor

PDGF can promote angiogenesis and regulates cell growth and differentiation.

It is a potent mitogen for mesenchymal derived cells, including smooth muscle cells and glial cells.

It has a tyrosine kinase receptor.

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Transforming Growth Factor

TGF alpha induces epithelial development. It is also involved in tissue regeneration, cell

differentiation, embryonic development and immune system regulation.

It is produced in macrophages, the brain and in keratinocytes.

TGF is upregulated in some forms of cancer.

Page 71: Regeneration with Dr. David Steenblock

Vascular Endothelial Growth Factor

VEGF stimulates vasculogenesis and angiogenesis.

It creates new blood vessels during embryonic development, new blood vessels after injury and when other vessels are blocked, and new muscle after exercise.

VEGF is required for cancer metastasis and overexpression is seen in retinal diseases.

Page 72: Regeneration with Dr. David Steenblock

The Heart and Growth Factors

Angiogenesis and vasculogenesis are important factors in cardiovascular health.

Endothelial progenitor cells help to repair damaged and dying blood cells.

Platelet-derived growth factor receptor alpha cells can generate significant numbers of smooth muscle cells and endothelial cells.

Chong JJ, et al. Progenitor cells identified by PDGFR-alpha expression in the developing and diseased human heart. Stem Cells Dev 2013, Feb 7.

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The Heart and Growth Factors

Angiogenesis is increased by vascular endothelial growth factor, hepatocyte growth factor and insulin-like growth factor-1.

Natriuretic peptide, transforming growth factor-beta 1, cardiotrophin-1, urocortin, acetylcholine, insulin and carbon monoxide can help the heart to mimic post conditioning.Maslov, LN. et al. Trigger mechanism of adaptive phenomenon of ischemic heartpostconditioning. Ross Fiziol Zh Im I M Sechenova 2012; 98(9): 1053-69.

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The Heart and Growth Factors

Heparin and fibroblast growth factor-2 have been shown to reduce scarring in the infarcted mycardium.

There was reduced inflammation, fibrosis and cardiomyocyte death and greater cardiac contractibility.

Chu H, et al. The effect of a heparin-based coacervate of fibroblast growth factor-2 on scarring in the infarcted myocardium. Biomaterials 2013; 34(6): 1747-56.

Page 75: Regeneration with Dr. David Steenblock

The Heart and Growth Factors

Secretoneurin, an angiogenic factor, stimulates vascular endothelial growth factor and fibroblast growth factor receptor-3 in rats with myocardial infarction.

Albrecht-Schgoer K, et al. The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells. Circulation 2012; 126(21): 2491-501.

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The Heart and Growth Factors

Rats administered oxytocin for 2 weeks showed greater protection against myocardial infarction.

The oxytocin raised atrial natriuretic peptide levels, as well as p38-MAPK, Akt kinase and heat shock protein 27 in the left ventricular heart tissue.

Ondrejcakova M, et al. Prolonged oxytocin treatment in rats affects intracellular signaling and induced myocardial protection against infarction. Gen Physiol Biophys 2012; 31(3): 261-70.

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The Heart and Growth Factors

Cardiac function improved after acute myocardial infarction in rats that were given hepatocyte growth factor and vascular endothelial growth factor in a hydrogel.

Salimath AS, et al. Dual delivery of hepatocyte and vascular endothelial growth factors via a protease-degradable hydrogel improves cardiac function in rats. PLoS One 2012; 7(11): e50980.

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The Heart and Growth Factors

In addition to growth factors, both hematopoietic stem cells and mesenchymal stem cells release exosomes that improve myocardial function. Exosomes fuse with target cells, transferring specific miRNA molecules between the cells.

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The Heart and Growth Factors

Exosomes can also act as vectors for genetic information. They have been shown to establish a communication network among the cells.

Barile L, et al. Ultrastructural evidence of exosome secretion by progenitor cells in adult mouse myocardium and adult human cardiospheres. J Biomed and Biotech 2012. Article ID 354605 (Epub ahead of print)

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The Lungs

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The Lungs and Growth Factors

Fibroblast growth factor-7 (known as keratinocyte growth factor) enhances the repair of injured alveolar epithelium in endotoxin-induced lung injury in rats.

Prostaglandin E2 re-programs alveolar macrophages to secrete anti-inflammatory interleukin-10.

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The Lungs and Growth Factors

Angiopoietin-1 (Ang), promotes angiogenesis and reduces endothelial permeability.

Mesenchymal stem cells secrete Angiopoietin-1 as well as FGF-7, prostaglandin E2 and Interleukin-10.

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The Lungs and Growth Factors

Mesenchymal stem cells also secrete an antimicrobial peptide, LL-37 that is upregulated from bacterial stimulation.

Lee JW, et al. Concise Review: Mesenchymal stem cells for actue lung injury: Role of paracrine soluble factors. Stem Cells 2011; 29(6): 913-919.

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The Lungs and Growth Factors

Hematopoietic stem cells along with fibroblast growth factor-7 (keratinocyte growth factor) was shown to stimulate epithelial cell proliferation and reduce bleomycin-induced pulmonary fibrosis.

Aguilar S, et al. Bone marrow stem cells expressing keratinocyte growth factor via an inducible lentivirus protects against bleomycin-induced pulmonary fibrosis. PLoS One 2009; 4(11): e8013.

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The Lungs and Growth Factors

Hematopoietic stem cells support the lung during ischemic conditions with VEGF, platelet-derived growth factor, insulin-like growth factor and fibroblast growth factor to support angiogenesis.

Lu J et al. Neovascularization and Hematopoietic stem cells. Cell Biochem Biophys 2011 Oct 30 (Epub ahead of print)

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The Lungs and Growth Factors

Autologous endothelial progenitor cells show positive effects against endotoxin-induced acute lung injury in rabbits.

Polymorphonuclear cell infiltration and hemorrhages in the lung tissue was decreased by the endothelial cells.

Nitric oxide and malondialdehyde were also inhibited.

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The Lungs and Growth Factors

Superoxide dismutase, interleukin-10, and VEGF were increased from the endothelial progenitor cells.

Interleukin-1β, E-selectin, intercellular adhesion molecule-1 and inducible nitric oxide synthase were reduced.

Cao JP, Autologous transplantation of peripheral blood-derived circulating endothelial progenitor cells attenuates endotoxin-induced acute lung injury in rabbits by direct endothelial repair and indirect immunomodulation. Anesthesiology 2012; 116(6): 1278-87.

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The Lungs and Growth Factors

Intermittent hypoxia, as seen with obstructive sleep apnea, was found to mobilize bone marrow derived very small embryonic-like stem cells (VSELs) in mice that promote organ repair.

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The Lungs and Growth Factors

More than 1100 unique genes were differentially expressed in the VSEL stem cells that activated organ-specific developmental programs.

Gharib SA, et al. Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem cells and activates developmental transcription programs in mice. Sleep 2010; 33(11): 1439-46.

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Wound Healing

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Wound Healing and Growth Factors

Non-healing wounds are a significant cause of disability, death and financial expense.

Mesenchymal and hematopoietic stem cells have been found to accelerate wound closure and enhance wound repair quality with increased tensile strength.

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Wound Healing and Growth Factors

With stimulation from bone morphogenetic protein-4, mesenchymal stem cells are able to produce K14+ keratinocytes.

VEGF promotes angiogenesis and vasculogenesis.

Epidermal growth factor, erythropoietin and stromal cell-derived factor-1α are also expressed by mesenchymal stem cells.

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Wound Healing and Growth Factors

Fibrin spray and collagen matrix systems with cultured autologous mesenchymal stem cells have also increased wound healing.

Chen JS, et al. Therapeutic potential of bone marrow-derived mesenchymal stem cells for cutaneous wound healing. Frontiers in Immunology 2012; 3: 192.

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Wound Healing and Growth Factors

The use of placental extract shows positive results for various skin conditions, including chronic wounds, pressure ulcer and burns.

Chakraborty PD et al. Human aqueous placental extract as a wound healer. J Wound Care 2009; 18(11): 462, 464-7.

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Alternatives in Growth Factor Production

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Alternatives in Growth Factors

There has been a shortage of human organs for transplantation. In 2011, over 111,000 Americans were on the waiting list for organ transplants.

An alternative that is gaining credibility is the use organs and growth factors from animals. This is called xenotransplantation.

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Alternatives in Growth Factors

According to the World Health Organization, xenotransplantation, animal to human, is defined as “living cells, tissues or organs of animal origin and human body fluids, cells, tissues or organs that have ex vivo with these living, xenogeneic materials.”

(http://www.who.int/transplantation/xeno/en)

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The History of Xenografts

The Papyrus of Ebers (1500 B.C.), the writings of Aristotle(384-322 B.C.) and Pliny the Elder (A.D. 23-79), all contained many preparations made from human and animal organs to treat diseases.

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The History of Xenografts

2400 years ago Hippocrates (460-370 BC) advocated that animal skin be used to cover human ulcers and burns.

Hippocrates also put forth the idea that a diseased organ could be treated by giving the patient, fresh, healthy tissue of the same type.

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The History of Xenografts

1762 - Dr. Hunter in England, and in 1849, Dr. von Berthold in Germany, implanted testes in castrated roosters and demonstrated positive responses.

In 1889 Dr. Brown-Sequard injected himself with testicular extract from guinea pigs and was “tremendously rejuvenated.”

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The History of Xenografts

June 13, 1920 – Dr. Serge Voronoff did an ape to human- testicular implant.

January 1928 – One thousand Surgeons participating in a medical conference held in Austria agreed that “The gland

transplantation operation devised

by Dr. Serge Voronoff afforded

transient regeneration.”

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The History of Xenografts

1920-1930sDr. Paul Niehans

“The Father of

Cell Therapy” and

xenotransplantation.

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The History of Xenografts

Type of operating room used by Dr Niehans to transplant organ tissues from fetal sheep obtained

via “C” Section to adjacent patients.

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The History of Xenografts

In 1964, Dr. Reemtsma transplanted a kidney from a chimpanzee into a patient with end-stage renal disease. The operation extended the patient’s life for nine months.

Denner, J and Ralf R. Tönjes. Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses. Clin Microbiol Rev 2012; 25(2): 318.

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Alternatives in Growth Factors

In 1995, researchers showed that hematopoietic-promoting factor and stem cell factor from the porcine kidney were able to proliferate mouse hematopoietic progenitor cells, granulocyte-macrophage colony-forming units, and erythropoietic burst-forming units.

Kashiwakura I et al. Effect of a hematopoietic promoting factor derived from porcine kidney on the proliferation of mouse hematopoietic hematopoietic progenitor cells in liquid culture. Biol Pharm Buill 1995; 18(11): 1476-81.

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Alternatives in Growth Factors

In collaboration with the International Xenotransplantation Association, the University Hospital Geneva and the World Health Organization, an international inventory has been established to collect basicdata on xenotransplantation procedures in humans. (http:www.humanxenotransplant.org)

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The International Human Xenotransplantation Inventory has found 29 human applications of xenotransplantation, including islets of Langerhans, kidney cells, chromaffin cells, embryonic stem cells, fetal and adult cells from various organs or the use of extracorporeal perfusion from hepatocytes, the liver, spleen or kidney.

Sgroi A, et al. International Human Xenotransplantation Inventory. Transplantation 2010; 90: 597-603.

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Porcine Research

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Alternatives in Growth Factors

Porcine neonatal islets of Langerhans with porcine Sertoli cells were administered to 12 children with type 1 diabetes (insulin-dependent) without immunosuppression.

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The authors reported a significant reduction in exogenous insulin requirements during the 4 year follow-up among six patients, two of whom became temporarily insulin-independent.

Valdes-Gonzalez R et al, Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets. Clin Exp Immunol 2010; 162(3): 537-42.

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Alternatives in Growth Factors

With the genetic modification of pigs, cell transplant studies such as those of pancreatic islets are leading to more hopeful results. The range of possibilities offered by this technology will be unlimited, making it possible for xenotransplantation to be a clinical reality soon.

Costa Valles C, Manez Mendiluce R. Transgenic organs and xenotransplants. Adv Exp Med Biol 2012; 741:73–88.

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Sheep Research

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Alternatives in Growth Factors

With sheep, the Center for Living Cell Therapy in Lenggries, Germany was started by Dr. Siegfried Block who had worked with Dr. Hans Niehans.

The Center raises 700 sheep in the high mountains, away from damaging environmental effects.

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Alternatives in Growth Factors

85 different fetal or neonatal organs are available for live sheep cells that are used to treat specific health functions.

The clinic offers cells to treat aging, impotence, Down’s syndrome, AIDS and many other conditions.

http://www.frischzellen-kur.de

Sgroi A, et al. International Human Xenotransplantation Inventory. Transplantation 2010; 90: 597-603.

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Rabbit Research

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Alternatives in Growth Factors

In Russia, the use of rabbit newborn pancreatic grafts with kidney extracts showed a survival rate of 75% in 26 type 1 (insulin-dependent) diabetic children. The results included insulin stabilization, reductions in glycoslyated hemoglobin, reduced exogenous insulin and a small increase in serum C-peptide.

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In diabetic nephropathy children, there was also a decrease in albuminuria from about 220 to 60 mg/day. (http://nikrrom.chat/ru/list1_en.htm)

Sgroi A, et al. International Human Xenotransplantation Inventory. Transplantation 2010; 90: 597-603.

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Alternatives in Growth Factors

As stem cell research has expanded, there have been organizations that promote rabbit fetal precursor stem cells

(BCRO: Bio-Cellular Research Organization in Russia and Eco-Ultrafiltrates in Europe).

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Rabbit progenitor cells have been used in clinical studies around the world for diabetes, immune deficiency disorders, neurological degeneration, cardiovascular disease, and genetic disorders in children.

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Article on rabbit progenitor cells and the diabetic retina:

Zubkova S.T., Danilova A.I., Kovpan N.A.: ("Condition of vessels of retina and of lower extremities in diabetic patients after transplantation of cultures of islet cells of pancreas"), Summary, in: Proceedings of 4th Congress of Ukrainian Endocrinologists, Kiev (now Ukraine), 1987. p. 153.

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The rabbit fetal progenitor cells have also been given 3 times a year to children with Down’s Syndrome.

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From Dr. Molnar’s article:

E. Michael Molnar, Gebrevnikova NV, Burkova MI, Sukhikh GT, Fisenko NA, Ionova AP: Influence of the transplantation of fetal tissue on the development of higher mental functions in children with Down Syndrome.

Klinicheskij Vestnik, 12 (4): 1995; 341.

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FCTI (Eco-ultrafilterates from Europe) is using ultrafiltration and nanotechnology to create rabbit derived progenitor cells and growth factors without the proteins.

Do these products actually promote regeneration?

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Alternatives in Growth Factors

The ready-to-use Eco-ultrafiltrates contain components up to a nominal molecular weight of 10 kDa – about 1/9th of the smallest virus known at this time.

The first ultra-filtrate for the skin and the mucosa was from a histological study by Dr. F. Leyh in 1981. Since then, the FCTI company was formed and more products have been created.

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Eco-ultrafiltrates have a variety of cell products that support the skin, mesenchyme, placenta, male and female revitalization, thymus, immune, kidney, liver, adrenal cortex, adrenal medulla, prostate, pituitary, pancreas, bone, cartilage and synovia, lungs, blood, spinal cord, heart, eye, colon, transfer factor, thyroid, etc.

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Growth Hormone

Growth hormone - 22,124 daltons. Even though structurally similar to growth

hormones from animals, only human and old world monkey growth hormones have significant effects on the human growth hormone receptor.

No animal product can be used as a substitute for human growth hormone.

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Alternatives in Growth Factors

Xenotransplantation businesses are expanding throughout the world.

xenograft organ extracts (porcine and sheep-ovine) are available and have been used in Germany for many years on patients.

In general, little side effects. No reported transmission of micro-organisms

when prepared in GMP lab.

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Our Treatment Program

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Bone Marrow Treatments

Our clinic offers autologous bone marrow stem cell therapies with the person’s own growth factors.

The FDA classifies the simple removal and re-injection of bone marrow as routine medical practice.

Culturing of the patient’s stem cells makes these a drug and can not be advertised.

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Bone Marrow Treatments

Optimum treatment today: Neupogen shots daily for 5 days, 14-15 days later bone marrow is aspirated

from each hip and given back intravenously, Gives much better results than simple bone

marrow but in people under 40, a simple bone marrow treatment is usually good.

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Fat Stem Cells

Fat stem cells have recently been classified by the FDA as drugs, so advertising the use of these for anything other than cosmetic purposes could be a problem.

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Treatments

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Treatments

After the transfusion,

the stem cells circulate

throughout the body to repair

or replace damaged and aging cells.

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Support for the Stem Cells

The stem cell treatments can benefit a variety of hard-to-treat conditions.

The elimination of toxins, infections and other problems before, during and after stem cell treatments (including checking for sleep apnea).

The use of hormones, growth factors and additional therapies enhances the results.

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Support for the Stem Cells

Each case is different and some may take more time to prepare for the procedure to achieve optimum results.

The combination of stem cell/progenitor cell therapies with electromagnetic therapy provides increased improvement for a longer time.

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Treatable Conditions

Osteoarthritis (DJD) Acute & chronic heart disease, heart attack Cerebral palsy Sports injuries Cartilage repair Spinal disc disorders GI disorders Kidney disorders

Diabetes I and II Eye disorders Autoimmune diseases Multiple sclerosis ALS Parkinson’s disease Dementia Huntington’s disease Other Genetic Disorders

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Together, we can make a

difference.

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For Further Information

Check out our websites and sign up for our newsletter at:

http://www.stemcellmd.org http://www.stemcelltherapies.org

My clinic toll free number is800-300-1063