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

Stem Cells: Myths, Facts, and EthicsStem Cells: Myths, Facts, and Ethics

Anthony D’Ascoli Anthony D’Ascoli PHI 2604PHI 2604

The ethical hot spots of stem cell researchThe ethical hot spots of stem cell research

Human embryonic stem cells isolated from Human 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 from Induced pluripotent stem cells derived from human skin cells. human skin cells.

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

Definition of stem cells:Definition of stem cells:

Self-renewalSelf-renewal

Multi-potencyMulti-potency

Lineage restricted Lineage restricted Limited self-renewalLimited self-renewal

TotipotentTotipotent TotipotentTotipotent TotipotentTotipotent

Differences between Differences 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 an Embryonic 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 by Adult cells emphasize on stability and need to be activated by

cues, e.g. injuries.cues, e.g. injuries.

Pluripotent ES cells

Source of ES cells

Human ES cells Human ES cells Human blastocyst Human blastocyst

Inner cell mass

Mouse fibroblasts feeder layer

DifferentiationES cells

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 Replacement Transplantation-Cell Replacement

Drug Development Drug Development

Organogenesis Organogenesis

Scientific Challenges of Using Human ES Cells: Scientific Challenges of Using Human ES Cells:

Challenges to cell-replacement and organ Challenges 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 studying Challenges 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 human Can not create the mutations corresponding to human diseasesdiseases





Somatic cell nuclear transfer (SCNT)Somatic cell nuclear transfer (SCNT)

For establishing and studying models of For establishing and studying models of human diseaseshuman diseases

For generating patient-specific For generating patient-specific cells/organs for transplantation and repaircells/organs for transplantation and repair

Therapeutic Cloning: Organogenesis

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

Example: ALS

D

B E

C F

A

Mark Denham & Richard Mollard

Not This





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 iPSCs2) iPSCs are induced by cancer genes therefore hinder their

use for therapies

“Reprogramming”





People in the US affected by diseases that may be People 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 AffectedCardiovascular diseasesCardiovascular diseases 58 Million58 MillionAutoimmune diseasesAutoimmune diseases 30 Million30 MillionDiabetesDiabetes 16 Million16 MillionOsteoporosisOsteoporosis 10 Million10 MillionCancerCancer 8.2 Million8.2 MillionAlzheimer's diseaseAlzheimer's disease 4 Million4 MillionParkinson's diseaseParkinson's disease 1.5 Million1.5 MillionBurns (severe)Burns (severe) 0.3 Million0.3 MillionSpinal cord injuriesSpinal cord injuries 0.25 Million0.25 MillionBirth defectsBirth defects 150,000 (per year)150,000 (per year)TotalTotal 128.4 Million 128.4 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).

The 1st ethical hot spot of stem cell researchThe 1st ethical hot spot of stem cell research


““In the case of embryonic stem cell In the case of embryonic stem cell research, the end that scientists hope to research, 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 end That this is a humanitarian and worthy end is not in dispute. The controversy is about is not in dispute. The controversy is about the means, namely, the consumption of the means, namely, the consumption of donated embryos.” donated embryos.” -- ISSCR website on stem cell ethics


International Guideline for Stem Cell Research (by International 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

The 3rd ethical hot spot of stem cell researchThe 3rd ethical hot spot of stem cell research


Protection of human subjectsProtection of human subjects Informed consentInformed consent Protection of genetic identity.Protection of genetic identity.

Other Related Ethical IssuesOther Related Ethical Issues

Ethical issues in human clinical trialsEthical issues in human clinical trialsInformed consent of patientsInformed consent of patientsProtection 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

How can scientists ensure ethical conduct How 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

Useful ResourcesUseful Resources

National Institute of Health resource for stem National Institute of Health resource for stem cells cells (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 Cell Guidelines 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)

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

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