1. Stem Cells What They Are and What They Do February 22, 2008

2. STEM CELLS HAVE 3 BASIC PROPERTIES 1 2 3 D1D1 D2D2........DnDn CAPABLE OF CAPABLE OFSELF-RENEWAL UNDIFFERENTIATED AND ABLE TO DIVIDE INDEFINITELY CAPABLE OF DIFFERENTIATION INTO CAPABLE OF DIFFERENTIATION INTO DIFFERENT CELL TYPES DIFFERENT CELL TYPES Adapted from Caltech 2000

3. Types of Stem Cells Adapted from www.nih.gov

4. Formation of Blastocyst

5. Creation of Embryonic Stem (ES) Cells

6. Derivation of Human ES Cells From Geron Inc.

7. Embryonic Stem (ES) Cells ES cell colony Feedercells

8. Heart Cells Derived from ES Cells

9. Examples of Potential Clinical Uses of Stem Cells Regenerate the heart after myocardial infarction. Regenerate the heart after myocardial infarction. Cure diabetes by transplanting cells that produce insulin into the pancreas Cure diabetes by transplanting cells that produce insulin into the pancreas Regenerate kidneys obviating the need for dialysis Regenerate kidneys obviating the need for dialysis Regenerate hair follicles in aging scientists Regenerate hair follicles in aging scientists Regenerate the nervous system in many disorders ( Parkinson’s Disease, stroke, spinal cord injury etc.) Regenerate the nervous system in many disorders ( Parkinson’s Disease, stroke, spinal cord injury etc.)

10. Problem: Like all transplanted tissues, transplanted stem cells may potentially be rejected by the host immune system. Problem: Like all transplanted tissues, transplanted stem cells may potentially be rejected by the host immune system. Problem: Genetic mismatches between donor and host tissues may lead to abnormal cell-cell signaling Problem: Genetic mismatches between donor and host tissues may lead to abnormal cell-cell signaling and/or dysregulation of organ function. and/or dysregulation of organ function.

11. Creation of ES Cells by Nuclear Transfer www.nih.gov

12. Somatic Cell Nuclear Transfer (“therapeutic cloning”)

13. Oocyte blastocyst somatic cell Create an ES cell line with the patient’s own genes (DNA)

14. Deriving Pluripotent Stem Cells from Skin Cells

16. Types of Stem Cells

17. MULTIPOTENT STEM CELLS EXIST IN BOTH EMBRYOS AND ADULTS STEM CELLS IN EMBRYO STEM CELLS IN ADULT NEWLY-FORMED TISSUES AND ORGANS Adapted from Caltech 2000 NATURALTURNOVERREGENER-ATION

18. Multipotent Stem Cells In each organ of the body, most cells types arise during development from an organ-specific stem cell. In each organ of the body, most cells types arise during development from an organ-specific stem cell. Most organs seem to have some stem cells remaining even in the adult. The existence of specific islet cell and cardiomyocyte precursors is controversial. Most organs seem to have some stem cells remaining even in the adult. The existence of specific islet cell and cardiomyocyte precursors is controversial. There is some “plasticity” i.e. fat stem cells or bone marrow stem cells can generate brain cells. However most apparent transdifferentiation in vivo actually reflects cell fusion. There is some “plasticity” i.e. fat stem cells or bone marrow stem cells can generate brain cells. However most apparent transdifferentiation in vivo actually reflects cell fusion.

19. Neural Stem Cells

20. Neurons

21. Oligodendrocytes (myelin)

22. Astrocytes

23. The same stem cell can generate all of the major cell types in the brain Clinical applications: Generation of neurons to repair areas of brain irrespective of the cause of the damage. Generation of neurons to repair areas of brain irrespective of the cause of the damage. Generation of oligodendroglia to facilitate remyelination (e.g. in multiple sclerosis or spinal cord injury). Generation of oligodendroglia to facilitate remyelination (e.g. in multiple sclerosis or spinal cord injury). Generation of astrocytes as a vehicle for gene therapy or drug therapy. Generation of astrocytes as a vehicle for gene therapy or drug therapy.

24. Question: How will a cellular microenvironment be created in vivo that fosters organ regeneration?

25. 11nm Collagen Fibril Architecture in Nanostructures is Useful to Regenerate Body Parts A nanoscale cylinder with highly ordered surface to deliver biological information--peptides S.I. Stupp Northwestern University

26. Mineral Nucleation Region Bioactive Region Crosslinkable Region Bioactive Peptide-Amphiphiles Hydrophobic Tail Science, 294, 1684 (2001) C10CCCCGGGS (P) RGD(-3)

27. Self-Assembly into Cylindrical Nanostructures

28. Scanning EM of Gel

29. Conclusions Stem cell biology promises to revolutionize the practice of medicine. Therapies will be come available for many previously untreatable diseases. Stem cell biology promises to revolutionize the practice of medicine. Therapies will be come available for many previously untreatable diseases. There are several types of stem cells that may potentially be used for such therapies. There are several types of stem cells that may potentially be used for such therapies. The embryonic stem cell has the most potential, but significant ethical/political issues remain to be resolved. The embryonic stem cell has the most potential, but significant ethical/political issues remain to be resolved.

30. Neurology – a vision Regenerative strategies will revolutionize the field of neurology. Disorders such as stroke, Parkinsons disease, spinal cord injury, traumatic brain injury, multiple sclerosis, and others will be treatable.