1. Jim Wells, Ph.D Assistant Professor Division of Developmental Biology Children’s Hospital Research Foundation of Cincinnati James.wells@cchmc.org 513-636-8767 Stem cell potential

2. Google “Hits” (x 1,000,000) 1 0.5 August 2005 2004 2003 2002 Google search for “human stem cell ethics” 2700% increase

3. (~10% type 1)

4. Stem cells Pluripotent embryonic stem cells PSCs Adult stem cells Also cord blood stem cells

5. Goal of all stem cell research Cure disease Adult stem cells stem cell PSC/ES cells in vitro Make Therapeutic Cells in vitro (in a petri dish) Therapeutic cell

6. Source of pluripotent/embryonic stem cells Human embryo 4 days after in vitro fertilization ~20 cells Eye of a needle 0.1mm 4/1000 th inch

7. Making pluripotent Stem Cell lines Donated surplus eggs from IVF clinics Cells will grow Indefinitely in a petri dish Make billions of copies Limitless supply of Potential therapeutic cells * Keep Frozen Other options Discard as medical waste * It is esimated that 400,000 surplus eggs are stored/frozen in the US Cell Line

8. Pluripotent Stem Cell lines Cell line 1 Wisconsin Göteborg Haifa Cell line 2 Cell line 3

9. Examples of what PSCs can become Potential limitless supply of any diseased cell Heart cells Bone cells Gut cells Brain neurons Spinal cord neurons Skin cells Blood cells Muscle cells (Crohne’s disease) (Oteoporosis) (Muscular Dystrophy) (Cardiovascular disease) (Anemia, Cancer) (Burns) (Paralysis) (Alzheimer’s Multiple Sclerosis)  -cells (Diabetes)

10. ~50,000,000,000,000 total cells Skin stem cells Blood stem cells No adult stem cell for  -cells in vivo X Examples of Adult stem cells Muscle stem cells ?

11. Comparison of stem cells Human adult SC’s Human PSC’s First isolated in November, 1998 Pluripotent - can become all cell types of the body Can multiply indefinitely in vitro Un-tested therapeutically First identified 4 decades ago Multipotent - can become some cell types of the body Limited replication in vitro Some therapeutics available

12. Future stem cell therapeutics Human adult SC’s Human PSC’s Diabetes Alzheimer’s Stroke Cardiovascular disease Autoimmune disease Parkinson’s Cancer Burns Spinal chord injury Birth defects ? ?

13. Human adult SC’s Alzheimer’s Cardiovascular disease Cancer Burns Spinal chord injury Future stem cell therapeutics ?

14. Human PSC’s Diabetes Stroke Autoimmune disease Parkinson’s Birth defects Future stem cell therapeutics ?

15. Future stem cell potential We don’t yet know which type of stem cell will ultimately cure these different diseases

16. Approved pluripotent Stem Cell lines Cell line 1 Wisconsin Göteborg Haifa Cell line 2 Cell line 3 There are between 11 and 20 approved lines available at the stem cell registry at the National Institutes of Health. Developed before August 2001

17. Current stem cell lines have limited therapeutic potential because: 1.Significant differences exist between cell lines 2.Grown with mouse cells as “feeders” 3.Little genetic diversity 4.Corporate funding/proprietary issues 5.Excludes use of patient-specific cell lines

18. 1.Significant differences between cell lines Physically different Genetically different/chromosomal abnormalities Multiply differently Differences in their ability to become therapeutic cell types?

19. Are these differences important? Wisconsin Göteborg Haifa Different lines may have different therapeutic potential, or none at all Hundreds of different cell types in the body affected by disease NOTHING  -cells nerves ? ? ?

20. 2.Human PSCs grown with mouse cells Feeder mouse cells provide important nutrients to help PSCs grow ALL existing cell lines were originally grown with mouse cells Possibility that mouse pathogens/viruses contaminate all cell lines Scientists have recently learned how to grow PSCs on human cells New “mouse free” cell lines have become available but are unapproved Mouse viruses? Mouse feeder cell Human PSC

21. Transplanted cells are rejected when they come from a genetically different donor Closely matched genetic background increases the probability of a successful transplantation More cell lines from diverse genetic groups are needed "No matter how we look at it, the federally approved cell lines are inadequate, we can do a lot of work with them, but we can't move into clinical trials or offer therapies with them.” J. Gearhart, Johns Hopkins Medical Institute, Panel discussing the clinical use of PSC/ES cells. 3.Little genetic diversity with existing cell lines

22. Proprietary issues Reduced scientific collaboration slows progress Less ethical oversight - full disclosure in academia "the absence of federal funding would mean a reduced role for federal oversight of the ethics of human embryonic stem cell research.” Ruth Faden, Ph.D., M.P.H. Executive Director of the Phoebe R. Berman Bioethics Institute at Johns Hopkins. Panel discussing the clinical use of PSC/ES cells. 4.Pitfalls of relying corporate development

23. Grow replacement cells in vitro Derive Patient-specific cell line Transplant cells therapeutic cloning Somatic cell Nuclear transfer 5. Patient specific stem cells: Somatic cell nuclear transfer/Therapeutic cloning No rejection of transplanted material Donated surplus eggs from IVF clinics

24. reproductive cloning Donated surplus eggs from IVF clinics Somatic cell Nuclear transfer Transfer to uterus Somatic cell nuclear transfer Reproductive cloning

25. reproductive cloning X X All scientists I’ve spoken with think reproductive cloning is immoral and should be illegal. Donated surplus eggs from IVF clinics Somatic cell Nuclear transfer Transfer to uterus Somatic cell nuclear transfer Reproductive cloning