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Stem Cells: Myths, Facts, and Ethics

Stem Cells: Myths, Facts, and Ethics. Anthony D’Ascoli PHI 2604. The ethical hot spots of stem cell research. Human embryonic stem cells isolated from blastocyst stage human embryos Cloning by somatic nuclear transfer Induced pluripotent stem cells derived from human skin cells.

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Stem Cells: Myths, Facts, and Ethics

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  1. Stem Cells: Myths, Facts, and Ethics Anthony D’Ascoli PHI 2604

  2. The ethical hot spots of stem cell research • Human embryonic stem cells isolated from blastocyst stage human embryos • Cloning by somatic nuclear transfer • Induced pluripotent stem cells derived from human skin cells.

  3. Part I: The myths and facts of stem cell researchPart II: The ethics of stem cell research

  4. Definition of stem cells: • Self-renewal • Multi-potency

  5. Totipotent Totipotent Totipotent Lineage restricted Limited self-renewal

  6. Differences between embryonic stem cells and adult stem cells • They have different self-renewal capabilities • Embryonic stem cells: near indefinite self-renewal • Adult stem cells: limited self-renewal • They have different differentiation potentials • .Embryonic stem cells: differentiate into all cell types in an organism • Adult stem cells: differentiate into restricted cells types. • They differ in how they respond to external stimuli • Embryonic stem cells are readily to change upon stimulation • Adult cells emphasize on stability and need to be activated by cues, e.g. injuries.

  7. Source of ES cells Pluripotent ES cells

  8. Human ES cells Human blastocyst Inner cell mass Mouse fibroblasts feeder layer

  9. ES cells Differentiation

  10. Applications of Human pluripotent stem Cells • Basic Knowledge of Human Development • Models of Human Disease • Transplantation-Cell Replacement • Drug Development • Organogenesis

  11. Scientific Challenges of Using Human ES Cells: Challenges to cell-replacement and organ transplantation therapies: • Lack of cell type specific differentiation • Possible tumor formation • Immune rejection by recipients Challenges to ES cells as models for studying human diseases Do not know the genes responsible for the diseases Can not create the mutations corresponding to human diseases

  12. The ethical hot spots of stem cell research • Human embryonic stem cells isolated from blastocyst stage human embryos • Cloning by somatic nuclear transfer • Induced pluripotent stem cells derived from human skin cells.

  13. Somatic cell nuclear transfer (SCNT) • For establishing and studying models of human diseases • For generating patient-specific cells/organs for transplantation and repair

  14. Therapeutic Cloning: Organogenesis

  15. Therapeutic cloning: Studying Mechanisms of Diseases Example: ALS Human ES Cells: Studying the Cellular and Molecular Mechanisms of Disease

  16. A D B E C F Mark Denham & Richard Mollard

  17. Not This

  18. The ethical hot spots of stem cell research • Human embryonic stem cells isolated from blastocyst stage human embryos • Cloning by somatic nuclear transfer • Induced pluripotent stem cells derived from human skin cells.

  19. “Reprogramming” induced pluripotent cells (iPSC) A combination of several genes can re-program skin fibroblasts into pluripotent cells • Why iPSC can not replace ESC research: • Studying ESCs is critical for understanding iPSCs • iPSCs are induced by cancer genes therefore hinder their use for therapies (Takahashi and Yamanaka Cell 2007, Yu Science 07, Cowan Science 07, Wernig Nature 07, Okita Nature 07)

  20. The ethical hot spots of stem cell research • Human embryonic stem cells isolated from blastocyst stage human embryos • Cloning by somatic nuclear transfer • Induced pluripotent stem cells derived from human skin cells.

  21. People in the US affected by diseases that may be helped by stem cell research Condition Number of Persons Affected Cardiovascular diseases 58 Million Autoimmune diseases 30 Million Diabetes 16 Million Osteoporosis 10 Million Cancer 8.2 Million Alzheimer's disease 4 Million Parkinson's disease 1.5 Million Burns (severe) 0.3 Million Spinal cord injuries 0.25 Million Birth defects 150,000 (per year) Total 128.4 Million -------------------------------------------------------------------------------------- Data from the Patients' Coalition for Urgent Research, Washington, DC (according to Perry, Ref. 267).

  22. The 1st ethical hot spot of stem cell research • Human embryonic stem cells isolated from blastocyst stage human embryos “In the case of embryonic stem cell research, the end that scientists hope to achieve is the relief of human suffering. That this is a humanitarian and worthy end is not in dispute. The controversy is about the means, namely, the consumption of donated embryos.” -- ISSCR website on stem cell ethics

  23. The 2nd ethical hot spot of stem cell research • Cloning by somatic nuclear transfer International Guideline for Stem Cell Research (by ISSCR Stem Cell Ethics Committee): Reproductive cloning is prohibited!!!

  24. The 3rd ethical hot spot of stem cell research • Induced pluripotent stem cells derived from human skin cells. • Protection of human subjects • Informed consent • Protection of genetic identity.

  25. Other Related Ethical Issues • Ethical issues in human clinical trials • Informed consent of patients • Protection of human subjects. • Protection of human genetic and cellular materials • Creating human/animal hybrid stem cells • Ethical issues in animal research. • Honest and integrity in biomedical research

  26. How can scientists ensure ethical conduct in stem cell research • Education for researchers • Routine emphasis by principle investigators • Emphasis by funding agencies • Classes and seminars • Education for the public • Understand the importance of research • Understand that scientists are under ethical guidance • Communication and open dialogue • Understand each others’ opinion • Reach a rationale common ground. • Last step: Legal reinforcement

  27. Useful Resources • National Institute of Health resource for stem cells (http://stemcells.nih.gov) • International Society for Stem Cell Research: “Guidelines for the Conduct of Human Embryonic Stem Cell Research (www.isscr.org)” • National Academy of Science: “Guidelines for human embryonic stem cell research” (http://www.nap.edu/openbook.php?isbn=0309096537)

  28. On March 9, 2009, President Obama issued Executive Order 13505, entitled "Removing Barriers to ResponsibleResearch Involving Human Stem Cells."

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