Stem Cells: Myths, Facts, and Ethics

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Stem Cells Myths, Facts, and Ethics

• Xinyu Zhao PhD
• Assistant Professor
• UNM School of Medicine
• Department 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 from human
  skin cells.

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Part I The myths and facts of stem cell
researchPart II The ethics of stem cell
research
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• Definition of stem cells
• Self-renewal
• Multi-potency

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Totipotent
Totipotent
Totipotent
Lineage restricted Limited self-renewal
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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.

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Source of ES cells
Pluripotent ES cells
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Human ES cells
Human blastocyst
Inner cell mass
Mouse fibroblasts feeder layer
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ES cells
Differentiation
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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 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

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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 from human
  skin cells.

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Somatic cell nuclear transfer (SCNT)

• For establishing and studying models of human
  diseases
• For generating patient-specific cells/organs for
  transplantation and repair

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Therapeutic
Cloning Organogenesis
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Therapeutic cloning Studying Mechanisms of
Diseases Example ALS
Human ES Cells Studying the Cellular and
Molecular Mechanisms of Disease
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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 from human
  skin cells.

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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)
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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 from human
  skin cells.

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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).

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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
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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!!!

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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 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

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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

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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?isbn0309096537)

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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 !