Exploring Stem Cell Research: Past, Present, and Future Perspectives

1. Stem Cells

2. Importance of Stem Cell Research

3. Stem Cell History 1998 - Researchers first extract stem cells from human embryos 1999 - First Successful human transplant of insulin-making cells from cadavers 2001 - President Bush restricts federal funding for embryonic stem-cell research 2002 - Juvenile Diabetes Research Foundation International creates $20 million fund-raising effort to support stem-cell research 2002 - California ok stem cell research 2004 - Harvard researchers grow stem cells from embryos using private funding 2004 - Ballot measure for $3 Billion bond for stem cells

4. What is stem cell research? • Understand more about development, aging, disease • Experimental model systems • Prevent or treat diseases and injuries • Cell-based therapies • Pharmaceutical development • Includes testing and drug delivery

5. Outline of Objectives • Introduction to fertilization and embryonic development • What makes stem cells unique? • What are the different types of stem cells? • What are examples of stem cell research, therapies, and technologies? Conclusion and future directions

6. Conception in a dish Day 1 In the IVF procedure, sperm and eggs “interact” in a dish leading to insemination. They literally swim up to the egg and burrow toward the nucleus. The first one to get there wins, and all others are blocked out. Male fertility issue: Sometimes sperm cannot latch onto and penetrate the egg. They may choose to have Intra(within)-Cytoplasmic Sperm Injection (ICSI)

7. Intra-Cytoplasmic Sperm Injection

8. Intra-Cytoplasmic Sperm Injection

14. Embryonic Stem Cells

15. Stages of Embryogenesis cleavage 8-cell stage blastocyst Blastocyst inner mass cells

16. Blastocyst Diagram

17. At what point is this a fetus? • Days 7-14: Uterine implantation • Day 14: Three distinct layers begin to form (no more pluripotent stem cells) • Days 14-21: Beginning of future nervous system • Days 21-24: Beginning of future face, neck, mouth, and nose • Weeks 3-8: Beginning of organ formation This picture is Week 5 • Week 5-8+: Now it’s called a fetus (no consensus on a single timepoint)

18. Embryonic Development:Zebrafish model Keller et al. 2008

19. Introduction to fertilization and embryonic development • What makes stem cells unique? • What are the different types of stem cells? • What are examples of stem cell research, therapies, and technologies? • Conclusion and future directions

20. Stem Cell – Definition A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues

21. Stem Cell Characteristics -‘Blank cells’ (unspecialized) -Capable of dividing and renewing themselves for long periods of time (proliferation and renewal) -Have the potential to give rise to specialized cell types (differentiation)

22. Symmetric cell division

23. Asymmetric cell division • Self-renews • Differentiates Progenitor cell Stem cell Stem cell

24. DIFFERENTIATION DIFFERENTIATION  SELF – RENEWAL 

25. Kinds of Stem Cells

26. Totipotent This cell Can form the Embryo and placenta Pluripotent This cell Can just form the embryo Multi- potent Fully mature

27. Pluripotent Stem Cells –more potential to become any type of cell

28. Multipotent stem cells Multipotent stem cells – limited in what the cells can become

29. Introduction to fertilization and embryonic development • What makes stem cells unique? • What do stem cells look like? • What are the different types of stem cells? • What are examples of stem cell research, therapies, and technologies? • Conclusion and future directions

30. Introduction to fertilization and embryonic development • What makes stem cells unique? • What are the different types of stem cells? • What are examples of stem cell research, therapies, and technologies? • Conclusion and future directions

31. Kinds of Stem Cells • Embryonic stem cells • five to six-day-old embryo • Tabula rasa • Embryonic germ cells • derived from the part of a human embryo or fetus that will ultimately produce eggs or sperm (gametes). • Adult stem cells • undifferentiated cells found among specialized or differentiated cells in a tissue or organ after birth • appear to have a more restricted ability to produce different cell types and to self-renew.

32. Totipotent This cell Can form the Embryo and placenta Pluripotent This cell Can just form the embryo Multi- potent Fully mature

33. Adult Stem Cells An undifferentiated cells found among specialized or differentiated cells in a tissue or organ after birth • Skin • Fat Cells • Bone marrow • Brain • Many other organs & tissues

34. Induced Pluripotent Stem Cells

35. Bone Marrow Found in spongy bone where blood cells form Used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. treat patients diagnosed with leukemia, aplastic anemia, and lymphomas Need a greater histological immunocompatibility

36. Blood Cell Formation

37. Umbilical cord stem cells Also Known as Wharton’s Jelly Adult stem cells of infant origin Less invasive than bone marrow Greater compatibility Less expensive

38. Umbilical cord stem cells Three important functions: Plasticity: Potential to change into other cell types like nerve cells Homing: To travel to the site of tissue damage Engraftment: To unite with other tissues

39. Stem cells in the adult brain:Are they still working for us now?

40. Stem cells in mature skeletal muscle:Is there power still in our stem cells?

41. Matrix Molecules Self-Renewal Soluble Factors Other Cells Differentiation Signals to Stem Cells Little, et al. Chemical Reviews (2008).

42. Genetic engineering How do cells know what to become? Tissue therapy All cells in a person share the same genotype Yet eye cells differ from nose cells Central dogma of biology

43. Induced Pluripotent Stem (iPS) CellsGenetically engineering new stem cells Skin cells iPS cells

44. Recreating Pluripotency Image courtesy of Clontech

45. Induced Pluripotent Stem (iPS) CellsGenetically engineering new stem cells Skin cells iPS cells

46. Pros and Cons to iPS cell technology • Pros: • Cells would be genetically identical to patient or donor of skin cells (no immune rejection!) • Do not need to use an embryo • Cons: • Cells would still have genetic defects • One of the pluripotency genes is a cancer gene • Viruses might insert genes in places we don’t want them (causing mutations)

47. Introduction to fertilization and embryonic development • What makes stem cells unique? • What are the different types of stem cells? • What are examples of stem cell research, therapies, and technologies? • Conclusion and future directions

48. What are stem cell technologies? • Cloning technologies • Is human cloning a technology? • What is different about cloning embryonic stem cells? • Induced Pluripotent Stem cells • New ways to potentially avoid the use of embryos • Disease-specific stem cell lines created • The promise and potential pitfalls of this approach When does research actually become technology?

49. Experimental model systemHeart muscle cells beating in a petri dish! Videos by the Exploratorium

50. Bone marrow transplant:Example of adult stem cell-based therapy