stem cell technology and it's application, ethical issues in detail

Stem cells , types of stem cells , it's application and ethical issues of stem cells

1. What ARE stem cells ??

2. In the 1960's two Canadian scientists, Ernest McCullough and JamesTill , discovered that all living tissue stemmed from a single cell, hence the term stem cell . Stem Cells and The Future Of Regenerative Medicine (Paperback) Institute of Medicine (Corporate Author) (Washington, DC: National Academies Press, 2002).

3. What Are Stem Cells? Stem cells are the raw material from which all of the body’s mature, differentiated cells are made. Stem cells give rise to brain cells, nerve cells, heart cells, pancreatic cells, etc.

4. What are Stem Cells?

5. http://stemcells.nih.gov/info/scireport/chapter1.asp#figure1 + High capacity for proliferation + Very long telomeres + Totipotent and pluripotent abilities + Low risk for disease Embryonic stem cells - Originate from abortions or IVF - Possible changes of the cells - Generation of tumors - Public acceptance questionable

6. What Do Stem Cells Do? 10 million cells die in your body every minute of every day. Your own stem cells replace them so you can continue living. This is what stem cells do for a living. 6650-0018-002

7. What Do Stem Cells Do? Reduce Inflammation Reduce pain Differentiation into tissue Home in on injury sites Induce healing-regeneration 6650-0019-001

8. What are Stem Cells? Stem Cells are Primitive cells present in almost every tissue: Self Renewing Able to become different tissue types Trophic Factories – Growth Factors 6650-0018-002

9. What Cells Do We Use? 1 1 Varma et al, Stem Cells and Development 2007:91-104 (freshly isolated adipose). Repeated by Collas et al and Yoshimura et al. 6650-0018-002

10. Two Kinds of Stem Cells Embryonic (also called “pluripotent”) stem cells are capable of developing into all the cell types of the body. Adult stem cells are less versatile and more difficult to identify, isolate, and purify.

11. All Stem Cells Are Important All stem cells can help scientists learn how cells regenerate or repair injured cells, tissues and organs. Scientists need both types of stem cells for their research. Each cell type can help inform scientists on how we develop and how some diseases affect our cells.

12. Regeneration in Humans High Moderate Low

13. Why stem cell? The following stem cell characterisics make them good candidate for cell based therapies: 1-potential to be harvested from patients. 2-High capacity of proliferation in culture. 3-Ease of manipulation to replace existing non functioning genes via gene transfer methods. 4-Ability to migrate to host ’ s target tissues. 5-Ability to integrate into host tissues.

14. Stem cells have 4 main properties: 1-Unspecialized. 2- Self renewal. 3-Potency : Stem cells are either: Totipotent (e.g. fertilized ova). Pleuripotent(e.g. ES cells, EC cells and EG cells , the last two are less desirable for research). Multipotent (e.g. tissue stem cells). Unipotent (e.g. hepatocytes, skin and corneal stem cells). 4-Robust repopulation (functional, long term tissue reconstitution). And moreover the flexibility in expressing these characteristics and serial transplantability should be feasible .Cells that fulfill all these criteria are called "actual stem cells." The cells that possess these capabilities but do not express them are named "potential stem cells." (Potten and Loeffler, 1990 and Dabeva et al., 2003).

15. Why is Stem Cell Research So Important to All of Us? Stem cells allow us to study how organisms grow and develop over time. Stem cells can replace diseased or damaged cells that can not heal or renew themselves. We can test different substances (drugs and chemicals) on stem cells. We can get a better understanding of our “genetic machinery.”

16. Why stem cells? Shortage of donor organs for transplantation Fountain of youth Replace damaged cells with fresh ones Rejection by the immune system Our cells obtained and proliferated Emerging technologies that could be useful to learn more about the human body and disease

17. What’s So Special About Stem Cells? They have the potential to replace cell tissue that has been damaged or destroyed by severe illnesses. They can replicate themselves over and over for a very long time. Understanding how stem cells develop into healthy and diseased cells will assist the search for cures.

18. A little history of the stem cells 1895-First use of the word “ stem cell ” by Valentin Häcker —a cell in the early embryo of a crustacean. 1938-Hans Spemann published the results of his nuclear transfer experiments using salamander embryos (first CLONING ) 1960s: Scientists present evidence of ongoing stem cell activity in the brain. 1960s - Joseph Altman and Gopal Das present scientific evidence of adult, neurogenesis ongoing stem cell activity in the brain; their reports contradict Cajal 's "no new neurons" dogma and are largely ignored. 1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow. 1968: Bone marrow transplant between two siblings success- fully treats Severe Combined Immunodeficiency (SCID). 1978: Hematopoietic stem cells (which are responsible for creating all components of blood cells) are discovered in human cord blood. Important Discoveries in Stem Cell Research

19. continued- 1956/1968- Dr. Thomas /Dr. Good perform first successful bone marrow transplants. 1970-Leroy Stevens proposes the existence of pluripotent stem cells after observing strange cells in mouse embryos that formed teratomas. 1973-First recombinant DNA organism created through gene splicing-now bacteria can make human insulin and more! (Cohen and Boyer) 1981- Sir Martin Evans and Matthew Kaufman derive pluripotent stem cell lines from mouse embryos. 1981: Embryonic stem cells are culled from the inner cell mass of mice. The term e mbryonic stem cell is coined by scientist Gail Martin.

20. More history 1988-Hematopoietic (blood forming) stem cell identified in humans by Irving Weissman. 1992: Neural stem cells are cultured in vitro. 1997: Leukemia is found to originate in hematopoietic stem cells—the first direct evidence of cancer stem cells. 1998: The first human embryonic stem cell line is derived at the University of Wisconsin–Madison byJames Thomson and coworkers. 2001: The first early (four- to six-cell stage) human embryos are cloned at Advanced Cell Technology for the purpose of generating embryonic stem cells. 2005: Researchers at Kingston University in England discover cord-blood-derived embryonic-like stem cells (CBEs), which are found in umbilical cord blood. These cells are able to differentiate into more types of tissue than adult stem cells. 1997-First mammal cloned (first cloned animal was a frog in 1952) 1998-James Thomson from U of Wisconsin, isolates human embryonic stem cells 2001-US embryonic stem cell research policy established 2001-directed differentiation of hESCs in vitro . 2004-First cloned human embryonic stem cells reported by Hwang Woo-Suk of S. Korea-later this research was discredited.

21. Almost done! 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth. 2005-Human neural stem cells repair mouse spinal cords 2005-World’s first cloned dog, Snuppy, is born. 2006: Kazutoshi Takahashi and Shinya Yamanaka discover that pluripotent stem cells can be induced in rats. 2006: Scientists in England create the first-ever artificial liver cells using umbilical cord blood stem cells. 2007: Normal skin cells are found to be capable of being reprogrammed to an embryonic state in mice. 2007-California Institute for Regenerative Medicine begins to distribute grants for stem cell research 2007-Japanese and American scientist create embryonic stem cells in mice without destroying embryos! 2007-Primate cloned for first time 2007-Human skin cells reprogrammed into pluripotent stem cells. Yamanaka, Yu and Thomson. 2007: Human-induced pluripotent stem cells are created, making it possible to produce a stem cell from almost any other human cell instead of relying on embryos. . 2007: Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on mouse embryonic stem cells. 2008: Human embryonic stem cell lines are generated without destruction of the embryo.

22. Possible Uses of Stem Cell Technology Repair of defective cell types (Type 1 diabetes, Parkinson’s disease, heart disease, nerve damage) Replace tissues/organs? Study of embryology and diseases Development of new drugs

23. Cell-Based Therapy If your skin was burned in an accident , there would be layers of skin cells that die. Using stem cell techniques, scientists could take a skin cell from another area on your body or stem cell and grow new plates of skin tissue in a lab tissue culture dish to regenerate new skin cells for you. http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=HUMN164B&File_type=GIF

24. Source: “Stem Cells: A Primer”

25. Stem cell potential uses Drug testing Drug production insulin Study of disease progression Understanding embryonic development Regeneration and tissue engineering Organs for transplant http://www.cordbloodbank.com/future_potential_of_stem_cells.html

26. Future Applications Stem Cells may one day help scientists to regenerate cells lost in diseases like: Repair heart muscle after a heart attack Pancreas cells lost in diabetes Neurons lost in Alzheimer’s Retinal cells causing blindness Understand the cell growths of cancers Help organ transplantation

27. Diseases that are treated by stem cells are: 1) Acute Leukemia • Acute Lymphoblast Leukemia (ALL) • Acute Myelogenous Leukemia (AML) • Acute Biphenotypic Leukemia • Acute Undifferentiated Leukemia 2) Chronic Leukemia • Chronic Myelogenous Leukemia (CML) • Chronic Lymphocytic Leukemia (CLL) • Juvenile Chronic Myelogenous Leukemia (JCML) • Juvenile Myelomonocytic Leukemia (JMML) Syndromes • Myelodysplastic Syndromes • Amyloidosis • Chronic Myelomonocytic Leukemia (CMML) • Refractory Anemia (RA) • Refractory Anemia with Excess Blasts (RAEB) • Refractory Anemia with Excess Blasts in Transformation • (RAEB-T) • Refractory Anemia with Ringed Sideroblasts (RARS)

28. Disorders 1) Stem Cell Disorders • Aplastic Anemia (Severe) • Fanconi Anemia • Paroxysmal Nocturnal Hemoglobinuria • Congenital Cytopenia • Dyskeratosis Congenita 2) Myeloproliferative Disorders • Acute Myelofibrosis • Agnogenic Myeloid Metaplasia • Polycythemia Vera • Essential Thrombocythemia 3) Lymphoproliferative Disorders • Non-Hodgkin’s Lymphoma • Hodgkin’s disease • Prolymphocytic Leukemia 4) Phagocyte Disorders • Chediak-Higashi Syndrome • Chronic Granulomatous Disease • Neutrophil Actin Deficiency • Reticular Dysgenesis 5) Inherited Metabolic Disorders • Mucopolysaccharidoses (MPS) • Hurler’s Syndrome (MPS-IH) • Scheie Syndrome (MPS-IS) • Hunter’s Syndrome (MPS-II) • Sanfilippo Syndrome (MPS-III) • Morquio Syndrome (MPS-IV) • Maroteaux-Lamy Syndrome (MPS-VI) • Sly Syndrome, Beta-Glucuronidase Deficiency • Adrenoleukodystrophy • Mucolipidosis II (I-cell Disease) • Krabbe Disease • Gaucher’s Disease • Niemann-Pick Disease • Wolman Disease • Metachromatic Leukodystrophy 6) Histiocytic Disorders • Familial Erythrophagocytic Lymphohistiocytosis • Histiocytosis-X • Hemophagocytosis • Langerhans’ Cell Histiocytosis

29. 7) Inherited Immune System Disorders • Ataxia-Telangiectasia • Kostmann Syndrome • Leukocyte Adhesion Deficiency • DiGeorge Syndrome • Bare Lymphocyte Syndrome • Omenn’s Syndrome • Severe Combined Immunodeficiency • SCID with Adenosine Deaminase Deficiency • Absence of T & B Cells SCID • Absence of T Cells, Normal B Cell SCID • Common Variable Immunodeficiency • Wiskott-Aldrich Syndrome • X-Linked Lymphoproliferative Disorder Other Inherited Disorders • Lesch-Nyhan Syndrome • Cartilage-Hair Hypoplasia • Glanzmann Thrombasthenia • Osteopetrosis • Adrenoleukodystrophy • Ceroid Lipofuscinosis • Congenital Erythropoietic Porphyria • Sandhoff Disease 9) Plasma Cell Disorders • Multiple Myeloma • Plasma Cell Leukemia • Waldenstrom’s Macroglobulinemia • Amyloidosis Abnormalities 1) Inherited Platelet Abnormalities Congenital Thrombocytopenia 2) Inherited Erythrocyte Abnormalities • Beta Thalassemia Major • Sickle Cell Disease • Blackfan-Diamond Anemia • Pure Red Cell Aplasia Other Malignancies • Ewing Sarcoma • Neuroblastoma • Renal Cell Carcinoma • Retinoblastoma • Brain tumor • Ovarian Cancer • Small Cell Lung Cancer • Testicular Cancer

30. What Human Diseases are Currently Being Treated with Stem Cells? Parkinson’s Disease Leukemia (Bone Marrow Transplants) Skin Grafts resulting from severe burns Stem Cell Therapy has the Potential to : Regenerate tissues/organs Cure diseases like diabetes, multiple sclerosis, etc.

31. Scientific Stem Cell Challenges Stem cells represents a very small fraction of cells in tissue. 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.

32. Opportunities All stem cell technologies provide opportunities in model development target identification and development screening for novel therapeutics developmental biology Regenerative Medicine