Will Stem Cells Finally Deliver Without Controversy?

Keith Gary, Ph.D.Director of Program Development

Kansas City Area Life Sciences Institute

Olathe North Life Sciences1 February 2012

What’s the Buzz?

PROMISE

POLITICS

Promise

Politics

Ethical Dilemma

Right To Life Movement

Young Scientific Field – little data

Not Amenable to Sound Bytes

Sexual Reproduction

Stages of Development

The Blastocyst

3-5 days post-fertilizationInner cell mass = ~30 cells

Germ Layer

Ectoderm

Endoderm

Mesoderm

Fate of Embryonic Tissues

Organs and Tissues in AdultSkin epidermis, epithelium of mouth and rectum, cornea and lens of eye, nervous system, tooth enamel

Epithelium, digestive tract and respiratory system; liver, pancreas, thyroid; lining of urethra, bladder, reproductive system

Skeletal and muscular systems; circulatory & lymphatic systems; reproductive system (except germ cells); dermis of skin, lining of body cavity

Seminal Events

1981 – Mouse embryonic stem cells grown in lab

1998 – First human embryonic stem cell line

1978 – First successful in vitro fertilization

1985 – Drug stimulated superovulation

What is a Stem Cell?

Self-renewing undifferentiated cells with the ability to repair damaged tissue.

Early Stage Stem Cells(Embryonic)

Undifferentiated cells that arepluripotent and have the potential tobecome any type of tissue of the body.

Early Stage Stem Cells are Pluripotent

Produces stem cells genetically identical to donorNot a new individualNo fertilization

Early StageStem Cells

Somatic Cell Nuclear Transfer (SCNT)

Are The Blastocysts Identical?

IVF SCNT

Adult Stem Cells

Undifferentiated cells found in a tissue ororgan that are multipotent and canbecome more than one type of tissue,but not all types.

Contains > 10 trillion cells with 250 different cell typesSome tissues continually renew themselves from adult stem cells

The Human Body

Adult vs. Embryonic Stem Cells

ES ASPluripotent Multipotent

Limiting differentiation in culture is problematic

More stable, easier to manage

Potentially immortal, unlimited supply

Lose ability to proliferate and differentiate in culture

High ethical burden, uncertain legal status

Less moral ambiguity and controversy

Alzheimer’s DiseaseCancer

Diabetes (Type I) Heart Disease

Macular DegenerationOsteoarthritis

Parkinson’s DiseaseRheumatoid ArthritisSpinal Cord Injuries

Stroke

Potential Disease Targets

Dan Perry, Executive Director of CAMR. Science (2000) 287: 1423.

U.S. Disease & Injury Statistics

Spinal Injuries– Restore function to damaged spinal cords (successful

in tests with paralyzed rats - regained ability to walk).

Examples of Potential TreatmentsType I Diabetes

– Replace pancreatic cells to restore normal blood sugar.

Burn Treatment– Regenerate functional skin following severe burns.

Alzheimer’s & Other Neurological Diseases – Regenerate neural cells and restore brain/body

communication to alleviate symptoms of Alzheimer’s, ALS, multiple sclerosis & Parkinson’s.

How Does Stem Cell Research Relate to Human Cloning?

• Multiple examples of successful cloning efforts – Dolly: 1 out of 276 attempts – Mouse: 100 blastocysts transferred to wombs,

seventy-one were able to take, from which between five and sixteen fetuses developed, and eventually two or three live mice were born

• “Therapeutic Cloning”

Cloning Animals

be made illegal with substantive penalties and strict enforcement

Human Cloning Must

HumanCloning

Ethical Alternatives

Altered Nuclear Transfer

• William Hurlbut, Stanford

• Genetic alteration in adult nucleus that represses a protein necessary for trophoblast maintenance.

• Zygote unable to implant in uterus.

Ethical Alternatives

Blastomeres ESC

• Preimplantation Genetic Diagnosis - technique commonly used during IVF to detect genetic disorders.

• Long-term consequences have not been adequately addressed.

• Advanced Cell Technology report

Ethical Alternatives

Induced pluripotent stem cells (iPSCs)

• adult cells genetically reprogrammed to an embryonic stem cell–like state.

• Although iPSCs meet the defining criteria for pluripotent stem cells, it is not known if they differ from embryonic stem cells in clinically significant ways.

• express genes and factors important for maintaining the defining properties of embryonic stem cells.

Induced pluripotent stem cells (iPSCs)

What the scientific community knows about stem cells

• The most “plastic” cells are early stage• Some adult stem cells have

differentiative potential• Other sources exist (Fetal Cord Blood)• Current stem cell lines approved for

government funded studies are inadequate to drive research forward

Clinical Trials

Geron Initiates Clinical Trial of Human Embryonic Stem Cell-Based Therapy - October, 2010

FDA OKs 1st Embryonic Stem Cell TrialJanuary, 2009

Second human embryonic stem cell clinical trial to startNovember, 2010

FDA Delays Clinical Trial of Embryonic Stem Cells May 2008

Take Home Message

• Stem cells have great potential benefits for agriculture and biomedical sciences.

• Efficiencies are very low and research needs to be done before stem cells will be of benefit to society.

• Its important for scientists to be proactive and educate the general public, media and government.

Additional Information

• National Institutes of Health http://stemcells.nih.gov/info/basics/

• University of Wisconsin http://www.news.wisc.edu/packages/stemcells

• Coalition for the Advancement of Medical Research http://www.camradvocacy.org/stem_cell_news.cfm