Will Stem Cells Finally Deliver Without Controversy? Keith Gary, Ph.D. Director of Program Development Kansas City Area Life Sciences Institute Olathe North Life Sciences 1 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-fertilization Inner cell mass = ~30 cells

Germ Layer Ectoderm Endoderm Mesoderm Fate of Embryonic Tissues Organs and Tissues in Adult Skin 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 are pluripotent and have the potential to become any type of tissue of the body.

Early Stage Stem Cells are Pluripotent

Produces stem cells genetically identical to donor Not a new individual No fertilization Early Stage Stem Cells Somatic Cell Nuclear Transfer (SCNT)

Are The Blastocysts Identical? IVF SCNT

Adult Stem Cells Undifferentiated cells found in a tissue or organ that are multipotent and can become more than one type of tissue, but not all types.

Contains > 10 trillion cells with 250 different cell types Some tissues continually renew themselves from adult stem cells The Human Body

Adult vs. Embryonic Stem Cells ESAS PluripotentMultipotent 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 Disease Cancer Diabetes (Type I) Heart Disease Macular Degeneration Osteoarthritis Parkinson’s Disease Rheumatoid Arthritis Spinal Cord Injuries Stroke Potential Disease Targets

Dan Perry, Executive Director of CAMR. Science (2000) 287: 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 Treatments Type 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 Human Cloning

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 Trial January, 2009 Second human embryonic stem cell clinical trial to start November, 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 University of Wisconsin ells Coalition for the Advancement of Medical Research ws.cfm