zhao ethic sym 2009 for notes

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    Stem Cells: Myths, Facts, and Ethics

    Xinyu Zhao PhD

    Assistant Professor

    UNM School of MedicineDepartment of Neuroscience

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    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 fromhuman skin cells.

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    Part I: The myths and facts of stem cell research

    Part II: The ethics of stem cell research

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    Definition of stem cells:

    Self-renewal

    Multi-potency

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    Lineage restricted

    Limited self-renewal

    Totipotent

    Totipotent

    Totipotent

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    Differences betweenembryonic 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.

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    PluripotentES cells

    Source of ES cells

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    Human ES cellsHuman blastocyst

    Inner cell mass

    Mouse fibroblasts feeder layer

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    DifferentiationES cells

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    Applications of Human pluripotent stem Cells

    Basic Knowledge of Human Development

    Models of Human Disease

    Transplantation-Cell Replacement

    Drug Development

    Organogenesis

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    Scientific Challenges of Using Human ES Cells:

    Challenges to cell-replacement and organtransplantation therapies:

    Lack of cell type specific differentiation

    Possible tumor formation

    Immune rejection by recipients

    Challenges to ES cells as models for studying

    human diseasesDo not know the genes responsible for the diseases

    Can not create the mutations corresponding to human

    diseases

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    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 fromhuman skin cells.

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    Somatic cell nuclear transfer (SCNT)

    For establishing and studying models of

    human diseases

    For generating patient-specificcells/organs for transplantation and repair

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    Therapeutic Cloning: Organogenesis

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    Human ES Cells: Studying the Cellular and Molecular Mechanisms of DiseaseTherapeutic cloning: Studying Mechanisms of Diseases

    Example: ALS

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    D

    B E

    C F

    A

    Mark Denham & Richard Mollard

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    Not This

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    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 fromhuman skin cells.

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    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

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    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 fromhuman skin cells.

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    People in the US affected by diseases that may behelped by stem cell research

    Condition Number of Persons AffectedCardiovascular diseases 58 MillionAutoimmune diseases 30 MillionDiabetes 16 Million

    Osteoporosis 10 MillionCancer 8.2 MillionAlzheimer's disease 4 MillionParkinson's disease 1.5 MillionBurns (severe) 0.3 Million

    Spinal cord injuries 0.25 MillionBirth defects 150,000 (per year)Total 128.4 Million--------------------------------------------------------------------------------------Data from the Patients' Coalition for Urgent Research, Washington,

    DC (according to Perry, Ref. 267).

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    The 1st ethical hot spot of stem cell research

    Human embryonic stem cells isolated fromblastocyst stage human embryos

    In the case of embryonic stem cellresearch, 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 aboutthe means, namely, the consumption of

    donated embryos. -- ISSCR website on stem cell ethics

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    Cloning by somatic nuclear transfer

    International Guideline for Stem Cell Research (by

    ISSCR Stem Cell Ethics Committee):

    Reproductive cloning is prohibited!!!

    The 2nd ethical hot spot of stem cell research

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    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.

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    Other Related Ethical Issues

    Ethical issues in human clinical trialsInformed 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

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    How can scientists ensure ethical conductin 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

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    Useful Resources

    National Institute of Health resource for stemcells (http://stemcells.nih.gov)

    International Society for Stem Cell Research:Guidelines for the Conduct of Human Embryonic Stem CellResearch (www.isscr.org)

    National Academy of Science: Guidelines forhuman embryonic stem cell research(http://www.nap.edu/openbook.php?isbn=0309096537)

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    On March 9, 2009, President Obama issued

    Executive Order 13505, entitled

    "Removing Barriers to Responsible

    Research Involving Human Stem Cells."

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    Thank you !