Stem Cell Research at the NIH

What are the unique properties that make human embryonic stem cells (hESCs) special? hESCs have an unlimited capacity for self renewal in culture hESCs have the capability to differentiate into any adult cell type (under the right conditions)

Non-Embryonic Stem Cells Include Fetal, Umbilical Cord Blood, and Adult Stem Cells Found in many organs such as bone marrow, gut, skin, nervous system, and liver Relatively rare (1/1000 to 1/10,000) Limited capacity for self renewal in the laboratory Limited capacity for differentiation—usually limited to cell types in organ of origin

Have hESC’s or Adult Stem Cells Treated Any Human Disease? Although hESC are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its early stages since there discovery in 1998 and initiation of federal funding in August 9, Adult stem cells, such as blood-forming stem cells in bone marrow, are currently the only type of stem cell commonly used to treat human diseases such as leukemia, lymphoma and other inherited blood disorders.

Image of hESCs in Culture hESC Line Pictured – HSF-6

Intro To Human Development

August 9, :01 P.M. CDT THE PRESIDENT: Good evening. I appreciate you giving me a few minutes of your time tonight so I can discuss with you a complex and difficult issue, an issue that is one of the most profound of our time. The issue of research involving stem cells derived from human embryos is increasingly the subject of a national debate and dinner table discussions…

“As a result of private research, more than 60 genetically diverse stem cell lines already exist. They were created from embryos that have already been destroyed, and they have the ability to regenerate themselves indefinitely, creating ongoing opportunities for research. I have concluded that we should allow federal funds to be used for research on these existing stem cell lines, where the life and death decision has already been made.” President’s Policy

Eligibility Criteria for Federal Funding

NIH Stem Cell Registry

Worldwide Survey of Stem Cell Lines According to the journal Stem Cells there are over 400 hESC lines available More than 300 are ineligible for federally funded research More lines are being created overseas than in the United States

Recent Legislation H.R Research Enhancement Act of 2005 Passed House/Senate; Vetoed by President S Alternative Pluripotent Stem Cell Therapies Enhancement Act Passed Senate; Failed in the House S Fetus Farming Prohibition Act of 2006 Passed House/Senate; Signed into law

NIH Supports Research on Many Types of Stem Cells Early phase of research—breakthroughs with clinical relevance might emerge from research on many types of stem cells FY2005 investment in human adult stem cell research – Approximately $200 million FY2005 investment in human embryonic stem cell research – Approximately $40 million Promote growth in both areas in the future

The Immediate Challenge for NIH and hESC Research 1.Generate and characterize distribution quality human ES cell lines from the NIH Registry 2.Stimulate more research on basic biology 3.Train investigators to culture and use stem cells

Infrastructure Awards Awards to organizations with entries on NIH Stem Cell Registry available for Federal funds to develop into distribution-quality cell lines Two year period of support Nine awards for total of $6,953,815 Led to development of 21 hESC lines ready for shipment

National Stem Cell Bank (WiCell Research Institute) Ready source of hESCs in one location Compare and expand hESCs available to NIH-supported scientists Ensure consistent quality control Reduce cost to obtain cells listed on the NIH Stem Cell Registry  8 hESC lines available for distribution  Negotiations underway for additional lines from the providers.

NIH Intramural Research Several laboratories at NIH are currently using hESC in their research Expanding interest as cell line availability becomes more straightforward Creation of a stem cell characterization unit within Intramural Research Program at NIH –

NIH Stem Cell Unit

NIGMS Exploratory Centers for hESC Research Awards were made to multi-investigator teams to conduct research using hESCs at –Albert Einstein College of Medicine –The Burnham Institute –Mount Sinai School of Medicine –University of Michigan Medical Center –University of Wash/Fred Hutchinson Cancer Research Center –WiCell Research Institute The Exploratory Center P20 Grant can lead to a Specialized Center P50 application

Centers of Excellence for Translational Stem Cell Research Multidisciplinary teams of stem cell experts, clinical researchers, and transplant surgeons Speed translation of basic knowledge to clinical therapies for human disease Test adult and embryonic stem cell therapies for many diseases including blood cancers, kidney disease, and neurological disorders Awards made to UC-Davis and Northwestern University

Stem Cell Training Short-term Courses in hESC Cell Culture Techniques held at: –Burnham Institute –Children’s Hospital of Orange County –Jackson Laboratory –Technion-Israel Institute of Technology –University of Georgia –University of Minnesota –University of Pittsburgh/Magee-Women’s Research Institute

Recent Scientific Advances Using Stem Cells  Further Evidence that Human Embryonic Stem Cells May Help Treat Vision Loss ( Laboratory of R. Lanza, Cloning and Stem Cells 8: )  Signaling Molecules May Help Adult Brain Repair Itself Following a Stroke (Laboratory of R. McKay, Nature advance online publication )  Neurons Grown from Embryonic Stem Cells Restore Function in Paralyzed Rats (Laboratory of D. Kerr, Annals of Neurology 60: 32–44)

Recent Scientific Advances Using Stem Cells  Blood Stem Cells Are Already Used to Treat Disease (National Marrow Donor Program,  ESCs Cure Mouse Model of Hemophilia (Laboratories of O. Smithies and J. Frelinger, Proc Natl Acad Sci 102: )  Human Stem Cells Help Rats with Spinal Cord Injury (Laboratory of A.J. Anderson, Proc Natl Acad Sci 102: 14069–14074)

Recent Scientific Advances Using Stem Cells  Protein Responsible for Balancing Stem Cell Growth, Aging, and Cancer (Laboratory of S. Morrison, D. Scadden, and N. Sharpless, Nature Advanced Online Publication)  Transplanted Cells Improve Symptoms in a Monkey Model of Parkinson's Disease (Laboratory of N. Hashimoto, J Clin Invest 115: 102–109)  Scientists Generate Motor Neurons from hESC (Laboratory of S-C Zhang, Nature Biotechnology 23: 215–221)

NIH Stem Cell Internet Sites Stem Cell Information – NIH Stem Cell Registry –