1. Stem Cells Mark Ellinger, Ph.D., J.D. Bethlehem Presents Series July 17,2008 Mark Ellinger, Ph.D., J.D. Bethlehem Presents Series July 17,2008

2. Stem Cells What Are They? The term “stem cell” originated in the late 1800’s: lFertilized egg ● “Germ” cells and immortality lblood-forming cells (hematopoietic stem cells) Skin cells Cells, particularly stem cells: highly complex, poorly understood

3. Stem Cells Just one component of the “cytoskeleton”:

4. Stem Cells Cells that can continuously produce unaltered descendants, but also have the ability to produce descendants that have different, more restricted properties

5. Stem Cells

6. EMBRYONIC STEM CELLS Differentiation Potential: everything, including germ cells Immortal in culture Cancer potential? EMBRYONIC STEM CELLS Differentiation Potential: everything, including germ cells Immortal in culture Cancer potential?

7. Stem Cells

9. SOURCES: Normal or abnormal blastocyst Blastocyst produced by transplanting adult cell nucleus into enucleated egg (“therapeutic cloning”) Chimeric Animal/Human blastocysts? Induced Pluripotent Stem Cells (iPSC’s) SOURCES: Normal or abnormal blastocyst Blastocyst produced by transplanting adult cell nucleus into enucleated egg (“therapeutic cloning”) Chimeric Animal/Human blastocysts? Induced Pluripotent Stem Cells (iPSC’s)

10. Stem Cells “Adult” Stem Cells: Differentiation potential: varies Lifespan in culture: varies (some reported to be unlimited) Role in the Body? Progeria – a defect in stem cells? Affected by common drugs? (e.g., statins) Renewal/repair Cancer? “Adult” Stem Cells: Differentiation potential: varies Lifespan in culture: varies (some reported to be unlimited) Role in the Body? Progeria – a defect in stem cells? Affected by common drugs? (e.g., statins) Renewal/repair Cancer?

11. Stem Cells Sources of Adult Stem Cells 1)Umbilical cord (blood and tissue) 2)Placenta 3)Amniotic fluid 4)Bone Marrow 5)Fat 6)Muscle 7)Brain 8)Other Sources of Adult Stem Cells 1)Umbilical cord (blood and tissue) 2)Placenta 3)Amniotic fluid 4)Bone Marrow 5)Fat 6)Muscle 7)Brain 8)Other

12. Stem Cells What’s All the Excitement?

13. Stem Cells Animal studies: remarkable results to date Heart and blood vessel repair Parkinsons’s Disease Muscular dystrophy (To name just a few) Human clinical studies: pointing in the same direction (caution required!) Animal studies: remarkable results to date Heart and blood vessel repair Parkinsons’s Disease Muscular dystrophy (To name just a few) Human clinical studies: pointing in the same direction (caution required!)

14. Stem Cells Human Stem Cell Trials:  Heart attack (Osiris) (mesenchymal stem cells)  Graft-versus-host-disease (Osiris) (mesenchymal stem cells)  Breast reconstruction (Cytori) (stem cells from fat)  Female incontinence (U. Pittsburgh) (connective tissue and muscle stem cells)  Peripheral vascular disease (Indiana U.; Tufts) (adult bone marrow stem cells) (legs spared)  Spinal cord injury (Geron) (embryonic stem cells) Human Stem Cell Trials:  Heart attack (Osiris) (mesenchymal stem cells)  Graft-versus-host-disease (Osiris) (mesenchymal stem cells)  Breast reconstruction (Cytori) (stem cells from fat)  Female incontinence (U. Pittsburgh) (connective tissue and muscle stem cells)  Peripheral vascular disease (Indiana U.; Tufts) (adult bone marrow stem cells) (legs spared)  Spinal cord injury (Geron) (embryonic stem cells)

15. Stem Cells 7) Parkinson’s (Harvard, Yale, U. Colorado) (human neural stem cells into primates) 8) Batten’s Disease (childhood neural degeneration) (Stem Cells Inc.) (fetal neural stem cells) 9) Cure of recessive dystrophic epidermolysis bullosa (EB)? (Univ. Minnesota) (bone marrow/cord blood stem cells) 10) Joint and cartilage repair 10) Many others 7) Parkinson’s (Harvard, Yale, U. Colorado) (human neural stem cells into primates) 8) Batten’s Disease (childhood neural degeneration) (Stem Cells Inc.) (fetal neural stem cells) 9) Cure of recessive dystrophic epidermolysis bullosa (EB)? (Univ. Minnesota) (bone marrow/cord blood stem cells) 10) Joint and cartilage repair 10) Many others

16. Stem Cells Back to Embryonic Stem Cells: Where to draw the line? Back to Embryonic Stem Cells: Where to draw the line?

17. Stem Cells 1) Normal embryos produced to supply stem cells 2) Normal embryos produced for in vitro fertilization and frozen for storage 3) Same as (2), but with no one to claim them 4) Abnormal embryos discarded by in vitro fertilization clinics 5) “Dead” embryos but with a few viable cells (different from harvesting organs from accident victims?) 6) Embryos produced by transplantation of adult cell nuclei 7) Same as (6), but genetically engineered to stop developing at an early stage 8) Cells taken from normal embryos, leaving the embryos “intact” 9) Human/Animal chimeric embryos 1) Normal embryos produced to supply stem cells 2) Normal embryos produced for in vitro fertilization and frozen for storage 3) Same as (2), but with no one to claim them 4) Abnormal embryos discarded by in vitro fertilization clinics 5) “Dead” embryos but with a few viable cells (different from harvesting organs from accident victims?) 6) Embryos produced by transplantation of adult cell nuclei 7) Same as (6), but genetically engineered to stop developing at an early stage 8) Cells taken from normal embryos, leaving the embryos “intact” 9) Human/Animal chimeric embryos

18. Stem Cells Will iPSC’s solve the ESC dilemma?

19. Stem Cells Thanks for Listening! Questions? Thanks for Listening! Questions?