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    • 1. Stem Cells: Myths, Facts, and EthicsStem Cells: Myths, Facts, and Ethics Xinyu Zhao PhDXinyu Zhao PhD Assistant ProfessorAssistant Professor UNM School of MedicineUNM School of Medicine Department of NeuroscienceDepartment of Neuroscience
    • 2. The ethical hot spots of stem cell researchThe ethical hot spots of stem cell research Human embryonic stem cells isolated fromHuman embryonic stem cells isolated from blastocyst stage human embryosblastocyst stage human embryos Cloning by somatic nuclear transferCloning by somatic nuclear transfer Induced pluripotent stem cells derived fromInduced pluripotent stem cells derived from human skin cells.human skin cells.
    • 3. Part I: The myths and facts of stem cell researchPart I: The myths and facts of stem cell research Part II: The ethics of stem cell researchPart II: The ethics of stem cell research
    • 4. Definition of stem cells:Definition of stem cells:  Self-renewalSelf-renewal  Multi-potencyMulti-potency
    • 5. Lineage restrictedLineage restricted Limited self-renewalLimited self-renewal TotipotentTotipotentTotipotentTotipotentTotipotentTotipotent
    • 6. Differences betweenDifferences between embryonic stem cells and adult stem cellsembryonic stem cells and adult stem cells They have different self-renewal capabilitiesThey have different self-renewal capabilities  Embryonic stem cells: near indefinite self-renewalEmbryonic stem cells: near indefinite self-renewal  Adult stem cells: limited self-renewalAdult stem cells: limited self-renewal They have different differentiation potentialsThey have different differentiation potentials  ..Embryonic stem cells: differentiate into all cell types in anEmbryonic stem cells: differentiate into all cell types in an organismorganism  Adult stem cells: differentiate into restricted cells types.Adult stem cells: differentiate into restricted cells types. They differ in how they respond to external stimuliThey differ in how they respond to external stimuli  Embryonic stem cells are readily to change upon stimulationEmbryonic stem cells are readily to change upon stimulation  Adult cells emphasize on stability and need to be activated byAdult cells emphasize on stability and need to be activated by cues, e.g. injuries.cues, e.g. injuries.
    • 7. Pluripotent ES cells Source of ES cells
    • 8. Human ES cellsHuman ES cellsHuman blastocystHuman blastocyst Inner cell mass Mouse fibroblasts feeder layer
    • 9. Differentiation ES cells
    • 10. Applications of Human pluripotent stem CellsApplications of Human pluripotent stem Cells Basic Knowledge of Human DevelopmentBasic Knowledge of Human Development Models of Human DiseaseModels of Human Disease Transplantation-Cell ReplacementTransplantation-Cell Replacement Drug DevelopmentDrug Development OrganogenesisOrganogenesis
    • 11. Scientific Challenges of Using Human ES Cells:Scientific Challenges of Using Human ES Cells: Challenges to cell-replacement and organChallenges to cell-replacement and organ transplantation therapies:transplantation therapies: Lack of cell type specific differentiationLack of cell type specific differentiation Possible tumor formationPossible tumor formation Immune rejection by recipientsImmune rejection by recipients Challenges to ES cells as models for studyingChallenges to ES cells as models for studying human diseaseshuman diseases Do not know the genes responsible for the diseasesDo not know the genes responsible for the diseases Can not create the mutations corresponding to humanCan not create the mutations corresponding to human diseasesdiseases
    • 12. The ethical hot spots of stem cell researchThe ethical hot spots of stem cell research Human embryonic stem cells isolated fromHuman embryonic stem cells isolated from blastocyst stage human embryosblastocyst stage human embryos Cloning by somatic nuclear transferCloning by somatic nuclear transfer Induced pluripotent stem cells derived fromInduced pluripotent stem cells derived from human skin cells.human skin cells.
    • 13. Somatic cell nuclear transfer (SCNT)Somatic cell nuclear transfer (SCNT) For establishing and studying models ofFor establishing and studying models of human diseaseshuman diseases For generating patient-specificFor generating patient-specific cells/organs for transplantation and repaircells/organs for transplantation and repair
    • 14. Therapeutic Cloning: Organogenesis
    • 15. Human ES Cells: Studying the Cellular and Molecular Mechanisms of Disease Therapeutic cloning: Studying Mechanisms of Diseases Example: ALS
    • 16. D B E C F A Mark Denham & Richard Mollard
    • 17. Not This
    • 18. The ethical hot spots of stem cell researchThe ethical hot spots of stem cell research Human embryonic stem cells isolated fromHuman embryonic stem cells isolated from blastocyst stage human embryosblastocyst stage human embryos Cloning by somatic nuclear transferCloning by somatic nuclear transfer Induced pluripotent stem cells derived fromInduced pluripotent stem cells derived from human skin cells.human skin cells.
    • 19. induced pluripotent cells (iPSC) A combination of several genes can re-program skin fibroblasts into pluripotent cells (Takahashi and Yamanaka Cell 2007, Yu Science 07, Cowan Science 07, Wernig Nature 07, Okita Nature 07) Why iPSC can not replace ESC research: 1) Studying ESCs is critical for understanding iPSCs 2) iPSCs are induced by cancer genes therefore hinder their use for therapies “Reprogramming”
    • 20. The ethical hot spots of stem cell researchThe ethical hot spots of stem cell research Human embryonic stem cells isolated fromHuman embryonic stem cells isolated from blastocyst stage human embryosblastocyst stage human embryos Cloning by somatic nuclear transferCloning by somatic nuclear transfer Induced pluripotent stem cells derived fromInduced pluripotent stem cells derived from human skin cells.human skin cells.
    • 21. People in the US affected by diseases that may bePeople in the US affected by diseases that may be helped by stem cell researchhelped by stem cell research ConditionCondition Number of Persons AffectedNumber of Persons Affected Cardiovascular diseasesCardiovascular diseases 58 Million58 Million Autoimmune diseasesAutoimmune diseases 30 Million30 Million DiabetesDiabetes 16 Million16 Million OsteoporosisOsteoporosis 10 Million10 Million CancerCancer 8.2 Million8.2 Million Alzheimer's diseaseAlzheimer's disease 4 Million4 Million Parkinson's diseaseParkinson's disease 1.5 Million1.5 Million Burns (severe)Burns (severe) 0.3 Million0.3 Million Spinal cord injuriesSpinal cord injuries 0.25 Million0.25 Million Birth defectsBirth defects 150,000 (per year)150,000 (per year) TotalTotal 128.4 Million128.4 Million ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Data from the Patients' Coalition for Urgent Research, Washington,Data from the Patients' Coalition for Urgent Research, Washington, DC (according to Perry, Ref. 267).DC (according to Perry, Ref. 267).
    • 22. The 1st ethical hot spot of stem cell researchThe 1st ethical hot spot of stem cell research Human embryonic stem cells isolated fromHuman embryonic stem cells isolated from blastocyst stage human embryosblastocyst stage human embryos ““In the case of embryonic stem cellIn the case of embryonic stem cell research, the end that scientists hope toresearch, the end that scientists hope to achieve is the relief of human suffering.achieve is the relief of human suffering. That this is a humanitarian and worthy endThat this is a humanitarian and worthy end is not in dispute. The controversy is aboutis not in dispute. The controversy is about the means, namely, the consumption ofthe means, namely, the consumption of donated embryos.”donated embryos.” -- ISSCR website on stem cell ethics
    • 23. Cloning by somatic nuclear transferCloning by somatic nuclear transfer International Guideline for Stem Cell Research (byInternational Guideline for Stem Cell Research (by ISSCR Stem Cell Ethics Committee):ISSCR Stem Cell Ethics Committee): Reproductive cloning is prohibited!!!Reproductive cloning is prohibited!!! The 2nd ethical hot spot of stem cell researchThe 2nd ethical hot spot of stem cell research
    • 24. The 3rd ethical hot spot of stem cell researchThe 3rd ethical hot spot of stem cell research Induced pluripotent stem cells derived fromInduced pluripotent stem cells derived from human skin cells.human skin cells.  Protection of human subjectsProtection of human subjects  Informed consentInformed consent  Protection of genetic identity.Protection of genetic identity.
    • 25. Other Related Ethical IssuesOther Related Ethical Issues Ethical issues in human clinical trialsEthical issues in human clinical trials Informed consent of patientsInformed consent of patients Protection of human subjects.Protection of human subjects. Protection of human genetic and cellular materialsProtection of human genetic and cellular materials Creating human/animal hybrid stem cellsCreating human/animal hybrid stem cells Ethical issues in animal research.Ethical issues in animal research. Honest and integrity in biomedical researchHonest and integrity in biomedical research
    • 26. How can scientists ensure ethical conductHow can scientists ensure ethical conduct in stem cell researchin stem cell research Education for researchersEducation for researchers  Routine emphasis by principle investigatorsRoutine emphasis by principle investigators  Emphasis by funding agenciesEmphasis by funding agencies  Classes and seminarsClasses and seminars Education for the publicEducation for the public  Understand the importance of researchUnderstand the importance of research  Understand that scientists are under ethical guidanceUnderstand that scientists are under ethical guidance Communication and open dialogueCommunication and open dialogue  Understand each others’ opinionUnderstand each others’ opinion  Reach a rationale common ground.Reach a rationale common ground. Last step: Legal reinforcementLast step: Legal reinforcement
    • 27. Useful ResourcesUseful Resources National Institute of Health resource for stemNational Institute of Health resource for stem cellscells (http://stemcells.nih.gov)(http://stemcells.nih.gov) International Society for Stem Cell Research:International Society for Stem Cell Research: ““Guidelines for the Conduct of Human Embryonic Stem CellGuidelines for the Conduct of Human Embryonic Stem Cell Research (www.isscr.org)”Research (www.isscr.org)” National Academy of Science:National Academy of Science: “Guidelines for“Guidelines for human embryonic stem cell research”human embryonic stem cell research” (http://www.nap.edu/openbook.php?isbn=0309096537)(http://www.nap.edu/openbook.php?isbn=0309096537)
    • 28. On March 9, 2009, President Obama issuedOn March 9, 2009, President Obama issued Executive Order 13505, entitledExecutive Order 13505, entitled "Removing Barriers to"Removing Barriers to ResponsibleResponsible Research Involving Human Stem Cells."Research Involving Human Stem Cells."
    • 29. Thank you !Thank you !

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