stem cell research

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stem cell research is yet to be advanced , once fully developed can alleviate human suffering, this ppt reviews the contemporary evidence, pitfalls and challenges

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  • In order to be used clinically, human embryonic stem cells must be differentiated prior to use in patients. Undifferentiated stem cells could produce tumors and multiply unchecked within a patient, causing more problems than providing appropriate therapy. It is uncertain if conditions can be defined such that all embryonic stem cells differentiate into the correct cell type prior to therapeutic use. Complications caused by undifferentiated cells might not be discovered until years after the first clinical trials are begun. This differentiation problem is acknowledged on the International Society for Stem Cell Research website: "Scientists are still working on developing proper conditions to differentiate embryonic stem cells into specialized cells. As embryonic stem cells grow very fast, scientists must be very careful in fully differentiating them into specialized cells. Otherwise, any remaining embryonic stem cells can grow uncontrolled and form tumors." 1 Recently, three established stem cell lines were shown to exhibit abnormalities in chromosome number and structure. 2 , 3 Obviously, stem cell lines must be checked periodically to make sure the cells do not become abnormal during continued culture. The use of abnormal cells in treatment of patients could result in indeterminate complications. References " Frequently Asked Questions ." International Society for Stem Cell Research. Draper, J.S., et al., "Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells," Nature Biotechnology December 7, 2003, advance online publication. C. Cowan et al. 2004. Derivation of Embryonic Stem-Cell Lines from Human Blastocysts. New England Journal of Medicine 350: 1353-1356.
  • Undifferentiated stem cells could produce tumors and multiply unchecked within a patient, causing more problems than providing appropriate therapy. According to a recent article ion the New England Journal of Medicine : "There are still many hurdles to clear before embryonic stem cells can be used therapeutically. For example, because undifferentiated embryonic stem cells can form tumors after transplantation in histocompatible animals, it is important to determine an appropriate state of differentiation before transplantation. Differentiation protocols for many cell types have yet to be established. Targeting the differentiated cells to the appropriate organ and the appropriate part of the organ is also a challenge.” Harvard scientists reported in the Proceedings of the National Academy of Sciences that five out of the 19 mice injected with embryonic stem cells developed tumors and died." 2 Stem cell lines will suffer the same tissue rejection problems as adult transplants. Once differentiated, these cells will express the HLA tissue antigens programmed by their parental DNA. These antigens must match those of the recipient or else tissue rejection will occur. An admission of the problem of immune rejection can be found from The Scientist : "[W]ithin the [embryonic stem cell] research community, realism has overtaken early euphoria as scientists realize the difficulty of harnessing ESCs safely and effectively for clinical applications. After earlier papers in 2000 and 2001 identified some possibilities, research continued to highlight the tasks that lie ahead in steering cell differentiation and avoiding side effects, such as immune rejection and tumorigenesis.” 1 References E. Phimister and J. Drazen. 2004. Two Fillips for Human Embryonic Stem Cells.” New England Journal of Medicine 350: 1351-1352. Bjorklund, L. M., R. Sanchez-Pernaute, et al. 2002 "Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model." Proceedings of the National Academy of Sciences 99: 2344-2349. Hunter, Philip. 2003. Differentiating Hope from Embryonic Stem Cells. The Scientist 17: 31 .
  • stem cell research

    1. 1. Stem cell research Dr.Veerendra Kumar C.M. MD.,DNB. Associate Professor VIMS,Bellary
    2. 2. VIMS
    3. 3. Human suffering…
    4. 4. <ul><li>Totipotent </li></ul><ul><li>Pluripotent </li></ul><ul><li>Multipotent </li></ul><ul><li>Oligopotent </li></ul>
    5. 5. What are stem cells? <ul><li>Self renewal in undifferentiated state </li></ul><ul><li>Potency to develop into different cells </li></ul>
    6. 6. Regenerative medicine <ul><li>Study of early human development </li></ul><ul><li>Therapeutic tool for various diseases </li></ul><ul><li>Develop and test new therapies </li></ul>
    7. 7. hESC (human embryonic stem cells) <ul><li>To study drug toxicity- </li></ul><ul><li>liver cells & cardiomyocytes derived from SC- useful to study drug toxicity Davila ,Toxico Sci 2004;79:214-23 </li></ul>
    8. 8. Types of stem cells <ul><li>Adult Embryonic </li></ul><ul><li>Adult - Bone marrow, </li></ul><ul><li>Cord blood </li></ul><ul><li>Embryonic - Unused IVF embryos </li></ul><ul><li>Pregnancy terminations </li></ul>
    9. 9. Embryonic V/S adult stem cells
    10. 10. Embryonic stem cells (ESC) <ul><li>Embryonic cells are pluripotent and virtually immortal. </li></ul>
    11. 11. Fetuses from pregnancy terminations <ul><li>Their ability to renew themselves is limited. </li></ul><ul><li>Animal studies have shown that it is more difficult to produce normal tissues from these cells. </li></ul>
    12. 12. Adult stem cells <ul><li>A person’s own stem cells should be the best source of cells for transplantation. </li></ul><ul><li>Adult stem cells will eventually substitute for embryonic stem cells. </li></ul>
    13. 13. Umbilical cord stem cells
    14. 14. Adult Stem Cells and Postnatal Stem Cells <ul><li>Advantages </li></ul><ul><ul><li>No ethical controversy. </li></ul></ul><ul><ul><li>None to minimal risk of immune rejection. </li></ul></ul><ul><ul><li>Reduced cost and time. </li></ul></ul><ul><ul><li>Genetic stability. </li></ul></ul><ul><li>Potential disadvantage </li></ul><ul><ul><li>?Limited plasticity </li></ul></ul><ul><ul><li>?Limited lifespan in culture, may carry defective gene </li></ul></ul>
    15. 15. FDA TRIALS USING ADULT OR CORD BLOOD STEM CELLS <ul><li>>70 current human clinical applications using adult stem cells </li></ul><ul><li>there are no current human clinical trials involving human embryonic stem cells </li></ul><ul><li>“ It is nearly certain that the [human] clinical benefits of the [embryonic stem cell] research are years or decades away. This is a message that desperate families and patients will not want to hear.” — Science, June 17, 2005 </li></ul>
    16. 17. Debate over hESC
    17. 18. Objections and concerns.. <ul><li>An embryo should be accorded full human </li></ul><ul><li>status from the moment of its creation </li></ul><ul><li>A first step on a ‘slippery slope’ towards human reproductive cloning. </li></ul>
    18. 19. Conservative vs. Liberal <ul><li>Conservative = Literal Translation of the Bible </li></ul><ul><li>Liberal = Compromising Translation of Bible </li></ul>
    19. 20. Question to consider: <ul><li>Is it ethical to delay research using embryonic stem cells until adult stem cells are fully capable of treating any disease? </li></ul>
    20. 21. Stem Cell Cultivation University of Wisconsin-Madison
    21. 22. Somatic Cell Nuclear Transfer (SCNT) technique used in ‘CLONING’ May be ethically acceptable as you are not using embryos by conventional methods
    22. 23. Novel methods <ul><li>Extraction of single blastomere without damaging embryo and developed into independent hESC lines Chung et al ,Nature 2006; 439:216-19 </li></ul><ul><li>Altered Nuclear Technique (ANT) genetically modifying the somatic nucleus so that induced pluripotent stem cells are produced meissener & Jaenisch Nature 2006;439:212-15 </li></ul>
    23. 24. First clinical trial using hESC <ul><li>GERON Co, 2005-2006 </li></ul><ul><li>Aldhous, Nature 2005;434:94-6 </li></ul>
    24. 25. Existing lines of hESC <ul><li>414 lines are available in 20 countries </li></ul><ul><li>Characterization of these lines is limited - only 49% of lines are published in peer reviewed journals Guhr et al Stem cells 2006;24:2187-91 </li></ul>
    25. 26. Derivation of hESC <ul><li>Frozen embryos from IVF cycle Expanded blastocyst – ICM immunosurgical isolation </li></ul><ul><li>Quality poor -2 nd quality embryos -cryoppreservation damages </li></ul><ul><li>Simon et al Fertil Steril 2005;83:246-9 </li></ul>
    26. 27. Maintenance of hESC <ul><li>Immortal cells in undifferentiated state </li></ul><ul><li>Optimal growth conditions for future therapeutic applications </li></ul><ul><li>Majority of hESC have been isolated and maintained in fetal calf serum and mouse embryonic fibroblasts as feeder cell layers (Xenoproteins and xenosupports) </li></ul>
    27. 28. Problems <ul><li>Transmission of interspecies virus transfer </li></ul><ul><li>Incorporation of foreign sugar molecule to hESC leading to immune response </li></ul><ul><li>It may also lead to impairment of cell function & tissue development Varki Am J Phys Anthropol Suppl 2001 </li></ul>
    28. 29. Research focus is on…. <ul><li>Use of human components instead of animal sources to avoid zoonosis </li></ul><ul><li>Fetal, adult muscle tissue, skin, Fallopian tube, endometrium, foreskin cells </li></ul><ul><li>Successful undifferentiated growth of hESC using xenobiotic –free feeder system </li></ul><ul><li>Richards ,Stem cells 2003;21:546-56 </li></ul>
    29. 30. Research focus is on… <ul><li>Feeder free culture system from recombinant sources Ludwig Nature Biotech 2006;24:185-7 </li></ul>
    30. 31. Differentiation <ul><li>Direct hESC to differentiate into specific cell lines - drug development - cell replacement therapeutics </li></ul><ul><li>Specific germ cell layers can be directed by adding specific growth factors </li></ul>
    31. 32. Scientific Stem Cell Challenges <ul><li>Stem cells represents a very small fraction of cells in tissue. </li></ul><ul><li>Isolate a small number of stem cells (finding a needle in a haystack). </li></ul><ul><li>Expand the number of stem cells for research and clinical applications. </li></ul><ul><li>Maintain genetic stability in culture and in recipient. </li></ul><ul><li>Culture media has to be free of animal protein. </li></ul><ul><li>Deliver cells to tissue of interest. </li></ul><ul><li>Stem cells have to be functional. </li></ul><ul><li>Avoid or restrict tissue rejection. </li></ul>
    32. 33. Challenges to Stem Cell/Cloning Research <ul><li>differentiation to the appropriate cell type(s) before using clinically. </li></ul><ul><li>Recently, chromosome abnormalities in three human ESC lines. </li></ul>
    33. 34. Challenges to Stem Cell/Cloning Research <ul><li>Stem cell development or proliferation must be controlled once placed into patients. </li></ul><ul><li>Possibility of rejection of stem cell transplants as foreign tissues is very high. </li></ul>
    34. 35. Beware <ul><li>Private companies promising wonders with stem cells - mostly in countries with unregulated laws Ilic D, Regenerative med 2006;1:1-4 </li></ul><ul><li>UKRAINE –capital of ESC ? </li></ul><ul><li>but the references they quote do not have international authenticity in peer reviewed journals </li></ul>

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