1. STEM CELLS: The Upside and Downside of Stem Cell Science Human ES cell colony: picture provided by Dr. Toshihiko Ezashi

2. Stem The main body or stalk of a plant The stock of a family lineage

4. Specialized (differentiated) cells Diploid, with 46 chromosomes Haploid with 23 chromosomes

5. Skin stem cell Neuronal stem cell Intestinal stem cell Bone marrow stem cell The human body consists of more than 10 trillion cells of more than 250 cell types

6. What are stem cells?  A stem cell has the ability to divide for indefinite number of divisions.  Stem cells give rise to more specialized cells when they differentiate.  There are three types of stem cell: unipotent, lineage specific stem cells, “adult” stem cells (multipotent), embryonic stem cells (pluripotent).

7. Real and Potential Applications of Stem Cells  Bone marrow transplantation  Transplantation medicine (diabetes, Parkinson’s Disease; stroke, arthritis, multiple sclerosis, heart failure; spinal cord lesions)  Drug testing  Genetic change  Other uses?

8. Source: NIH website “Stem cells: A Primer” UNIPOTENT STEM CELLS MNH P

9. ADULT STEM CELLS Undifferentiated, multipotent cells found in a differentiated tissue that can renew themselves and (with certain limitations) differentiate to yield all the specialized cell types of the tissue from which it originated, e.g stem cells from bone marrow that can give rise to all the blood cell types.

10. Stem Cells versus Progenitor Cells Niche Cells Stem Cells Progenitor cells Differentiated Cells Precursor cells

11. Source: NIH website “Stem cells: A Primer” PLURIPOTENT (Adult) STEM CELLS Do such cells exist? Where? Are they an alternative to pluripotent embryonic stem cells?

12. ADULT STEM CELLS HAVE BROAD HAVE BROAD THERAPEUTIC POTENTIAL (or do they?) THERAPEUTIC POTENTIAL (or do they?)

13. ADULT STEM CELLS HAVE LIMITED HAVE LIMITED THERAPEUTIC POTENTIAL THERAPEUTIC POTENTIAL

14. Embryonic stem cells What’s all the fuss about?

15. EMBRYONIC STEM CELLS Primitive (undifferentiated) cells, usually from the embryo, that have the potential to become a wide variety of specialized cell types.

16. Establishment of Human Embryonic Stem Cells  From “spare” IVF embryos  Therapeutic cloning, i.e. by somatic cell nuclear transfer  Induced pluripotent stem cells

17. Dominic Doyle

18. Bob Edwards and Patrick Steptoe

19. Over Three Million IVF and Thousands of PGD Babies have been Born!

20. SEXUAL REPRODUCTION REPRODUCTION

21. HUMAN ES CELLS First isolated in 1998 from spare blastocysts donated by an In Vitro Fertilization (IVF) program

22. Source: NIH website “Stem cells: A Primer”

23. CONCERN Production of new human ES cells will involve the destruction of thousands of human embryos

24. Facts  Every year hundreds of thousands of human embryos are created by in vitro fertilization procedures designed to allow infertile couples to have children. To obtain eggs for IVF, eggs are produced by “superovulation” procedures  Many more eggs are produced and fertilized than can possibly be used.  Result: embryos are discarded or stored indefinitely.

25. ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL LINES ADEQUATE FOR DEVELOPING THERAPIES?  Different lines have different properties: they don’t all behave the same.  Existing stem cells will never be useful for transplantation.  Transplantation demands a close “match” between the donor and the recipient, e.g. kidney transplantation. Hence there is a requirement for large numbers of cell lines with different transplantation antigens on their surfaces.

26. 1.How to direct their differentiation efficiently into specific cell types (e.g. pancreas, brain neurons). 2. How to deliver them efficiently for tissue repair. 3. How to prevent immune rejection. EMBRYONIC STEM CELLS FOR THERAPY

27. Establishment of Human Embryonic Stem Cells  From “spare” IVF embryos  Therapeutic cloning, i.e. by somatic cell nuclear transfer  Induced pluripotent stem cells

28. NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS

30. February 1997 Cloning of Dolly reported Cloning of Dolly reported

31. Somatic Cell Nuclear Transfer “Reproductive Cloning” Somatic Cell Nuclear Transfer “Reproductive Cloning” Sheep Cattle Goat Mule Pig Cat Mouse Rat Rabbit

32. Day 5 “Therapeutic ABILITY TO PRODUCE STEM CELLS GENETICALLY IDENTICAL TO PATIENT IDENTICAL TO PATIENT

33. HOW DOES THIS RELATE TO HUMAN CLONING???

35. CONCERN NUCLEAR TRANSPLANTATION WILL BE USED TO CLONE HUMAN BABIES.

36. NUCLEAR TRANSPLANTATION TO PRODUCE STEM CELLS NO EMBRYONIC OR FETAL DEVELOPMENT BEYOND 200 CELL STAGE (SIZE OF TIP OF PIN) NO TRANSFER TO UTERUS BLASTOCYST OR STEM CELLS ALONE CANNOT PRODUCE A NEW INDIVIDUAL

37. CONCERN Production of new human ES cells by somatic cell nuclear transfer will require an unlimited number of human oocytes from women donors

38. Day 5 CONCERN HUMAN EGG DONORS WILL BE EXPLOITED

39. Establishment of Human Embryonic Stem Cells  From “spare” IVF embryos  Therapeutic cloning, i.e. by somatic cell nuclear transfer  Induced pluripotent stem cells

40. Pluripotent stem cells from adult fibroblasts Nanog; Oct4 (POU domain transcription factor 5); Sox2, sex determining region Y-box 2 (SRY); Klf4 (Kruppel-like factor 4); c-Myc viral oncogene homolog; Lin28 homolog Lin28 Nanog Takahashi (Yamanaka et al., Cell,2007 Yu (Thomson) et al. Science 2007 Diagram from Zhares & Scholer, Cell 2007)

41. 0 23 GFP-PFF 30 Images of iPPC picked at day 30 20% O2 4% O2

42. Thank you

43. Issues  When does life begin? Missouri statutes indicate that human life begins at the moment of conception  The new constitutional amendment and what it means  But the sperm and the egg are alive  The transition from an embryo to a baby is a gradual one  Are embryos that cannot form a placenta or that are doomed to die before the differentiation of the main organ systems individuals?

44. ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL LINES ADEQUATE FOR DEVELOPING THERAPIES?

45. Some Questions  The status of hES cells. Are they the equivalent of embryos? Persons?  What are the objections to using spare embryos?  Are there alternatives to using hES cell lines for tissue replacement? Adult stem cells?  Can hES cells be produced by developing cell lines from a biopsy of an embryo?  Can embryos be created that lack any potential to develop into babies?