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

6. NIH hESC Awards FY2002-FY2003 9 Infrastructure Awards 27 Investigator-initiated Awards 88 Administrative Supplements 2 Pilot & Feasibility Projects (Beta Cell Consortium) 3 Postdoctoral Fellowships 6 Training Grants 5 Short Term Cell Culture Training Courses 3 Exploratory Center Research Grants

7. Infrastructure Awards Awards to organizations with entries on NIH hESC Registry available for Federal funds to develop into distribution-quality cell lines Two year period of support Nine awards for total of over $6M Led to development of twelve hESC lines ready for shipment with more to come in near future Program Announcement to be reissued

9. Program Announcements (PAs) Short-term Courses in Human Embryonic Stem Cell Culture Techniques –T15 Mechanism (Continuing Education Training) –Supported by 11 NIH Institutes –$1M direct costs committed (FY2002) –Three-year support ($150,000/year direct maximum) –Five awards have been made

10. Program Announcements Career Enhancement Award for Stem Cell Research (K18) and Career Development Award (K08, K23) NIDDK, NIAAA, NINR, NIAID, NHLBI Mid-career investigators, 6-24 month salary and $50,000 direct/year Training to use stem cells in research –grants.nih.gov/grants/guide/pa-files/PAR-02-069.html

11. Requests for Applications (RFAs) Exploratory Center Grants for hESC Research (NIGMS) (Letter of intent 2/13/03; receipt date 3/13/03) Multi-investigator teams to conduct multidisciplinary research using hESCs Infrastructure, growth and maintenance, biochemical/ molecular markers for hESCs, unique properties of hESCs, pilot studies leading to additional investigator-initiated research grant applications P20 Exploratory Center Grant, leading to P50 application $2M in 2003, funding 2-3 P20 grant applications for up to 3 years at $500,000 direct/year

12. Additional PAs/RFAs Innovative Concepts and Approaches to Developing Functional Tissues and Organs for Heart, Vascular, Lung, and Blood Applications (R21) (NHLBI) Plasticity of Human Stem Cells in the Nervous System (R01) (NINDS, NIA, NIMH, NHLBI) Basic and Applied Stem Cell Research for Arthritis and Musculoskeletal Diseases (RO1) (NIAMS) Stem Cells in Development/Repair of Orofacial Structures (NIDCR)

13. Additional PAs/RFAs Basic Research on Mesenchymal Cell Biology (NIA, NHLBI) Comprehensive Programs in Beta Cell Biology (NIDDK) Hematopoietic Cell Lineage Genome Anatomy (NIDDK) Cellular Repair Studies of the Auditory and Vestibular System (NIDCD) Research on Stem Cell Biology and Cell-based Therapies for Heart, Lung, Blood, and Sleep Disorders (NHLBI) Stem Cell Research for Alcohol-related Disorders (NIAAA)

14. NIH Intramural Research Nine 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

15. Human ES Cell Research Symposium Showcased research conducted and supported by NIH on June 13, 2003 Podium presentations and posters Workshops on topics of interest (cell culture, policy, intellectual property) Immediately after the GM Stem Cell Symposium on June 10-11, 2003

16. Highlights of Human ES Cell Research Progress Neural differentiation—protocol described to generate dopamine secreting neurons similar the midbrain neurons lost in Parkinson’s disease Pluripotency/Self Renewal—discovery of Nanog, a transcription factor that serves as a master regulator of pluripotent and self renewing state of human ES cells

17. Highlights of Human Es Cell Research (cont.) Hematopoietic differentiation—culture conditions being defined that promote specialization of human ES cells into blood forming cells Cardiac myocyte differentiation— functional characterization of atrial, ventricular, and nodal cardiac myocytes differentiated from human ES cells in culture

18. Research Advances using Other Types of Stem Cells Neuronal stem cells—discovery and characterization of a source of self- renewing neural progenitor cells in adult brain white matter Dental pulp stem cells—discovery of a pluripotent population of stem cells in dental pulp of deciduous teeth which can be cultured and divides

19. Research Advances using Other Types of Stem Cells (cont.) Hematopoietic stem cells—discovery that Wnt pathway can promote self renewal of hematopoietic stem cells in culture Multipotent Adult Progenitor Cells (MAPC)— bone marrow mesenchymal stem cell with capacity to self renew and become many different specialized cells Umbilical cord stem cells—research to define culture conditions that promotes expansion of cells obtained from a single unit in culture

20. Research advances (cont.) Human EG cells—in a rat model for ALS, scientists restored movement by transplanting EG cells, which secrete factors that promote survival of endogenous neurons Muscle stem cells (satellite cells)— scientists determined that the Wnt signaling pathway activates muscle formation

21. 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 FY2002 investment in human adult stem cell research--$170,745,000 FY2002 investment in human embryonic stem cell research--$10,689,000 Promote growth in both areas in the future

22. On the Research Horizon Definition of standardized human ES cell culture conditions that obviate the need for either mouse or human feeder cells Enabling tools and technologies to further characterize stem cells as they become specialized cells (specific antibodies, etc.) Define the molecular pathways that specify differentiation into different specialized cells

23. Horizon (cont.) Determine the factors/conditions critical for long-term survival and function of transplanted cells in a host Understand control of cell division— essential to expand cells before specialization, but must be tightly regulated after transplantation for therapy

24. NIH Stem Cell Web Sites Stem Cell Information –stemcells.nih.gov Human Embryonic Stem Cell Registry –escr.nih.go