Stem Cells: Myths, Facts, and Ethics

Xinyu Zhao PhD Assistant Professor UNM School of Medicine Department of Neuroscience

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.

Part I: The myths and facts of stem cell research

Part II: The ethics of stem cell research

Definition of stem cells: Self-renewal Multi-potency

Totipotent Totipotent

Lineage restricted Limited self-renewal

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.

Source of ES cells

Pluripotent ES cells

Human blastocyst
Inner cell mass

Human ES cells

Mouse fibroblasts feeder layer

Differentiation

ES cells

Applications of Human pluripotent stem Cells

Basic Knowledge of Human Development Models of Human Disease Transplantation-Cell Replacement Drug Development Organogenesis

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

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.

Somatic cell nuclear transfer (SCNT)

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

Therapeutic Cloning: Organogenesis

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

Example: ALS

Mark Denham & Richard Mollard

Not This

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.

induced pluripotent cells (iPSC) A combination of several genes can re-program skin fibroblasts into pluripotent cells

Reprogramming
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
(Takahashi and Yamanaka Cell 2007, Yu Science 07, Cowan Science 07, Wernig Nature 07, Okita Nature 07)

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.

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).

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

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!!!

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.

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

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

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)

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

Thank you !