The Immediate Challenge for NIH The Immediate Challenge for NIH and Human ES Cell Researchand Human ES Cell Research

Generate and characterize distribution Generate and characterize distribution quality human ES cell lines from the quality human ES cell lines from the NIH RegistryNIH RegistryStimulate more research on basic Stimulate more research on basic biologybiologyTrain investigators to culture and use Train investigators to culture and use stem cellsstem cells

NIH hESC AwardsNIH hESC AwardsFY2002-FY2003FY2002-FY2003

9 Infrastructure Awards 9 Infrastructure Awards

27 Investigator-initiated Awards27 Investigator-initiated Awards

88 Administrative Supplements88 Administrative Supplements

2 Pilot & Feasibility Projects (Beta Cell Consortium) 2 Pilot & Feasibility Projects (Beta Cell Consortium)

3 Postdoctoral Fellowships3 Postdoctoral Fellowships

6 Training Grants6 Training Grants

5 Short Term Cell Culture Training Courses5 Short Term Cell Culture Training Courses

3 Exploratory Center Research Grants3 Exploratory Center Research Grants

Infrastructure AwardsInfrastructure Awards

Awards to organizations with entries on NIH Awards to organizations with entries on NIH hESC Registry available for Federal funds to hESC Registry available for Federal funds to develop into distribution-quality cell linesdevelop into distribution-quality cell linesTwo year period of supportTwo year period of supportNine awards for total of over $6MNine awards for total of over $6MLed to development of twelve hESC lines ready Led to development of twelve hESC lines ready for shipment with more to come in near futurefor shipment with more to come in near futureProgram Announcement to be reissuedProgram Announcement to be reissued

Program Announcements (PAs)Program Announcements (PAs)

Short-term Courses in Human Embryonic Stem Short-term Courses in Human Embryonic Stem Cell Culture TechniquesCell Culture Techniques– T15 Mechanism (Continuing Education T15 Mechanism (Continuing Education

Training)Training)– Supported by 11 NIH InstitutesSupported by 11 NIH Institutes– $1M direct costs committed (FY2002)$1M direct costs committed (FY2002)– Three-year support ($150,000/year direct Three-year support ($150,000/year direct

maximum)maximum)– Five awards have been madeFive awards have been made

Program Announcements Program Announcements

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

Requests for Applications (RFAs)Requests for Applications (RFAs)

Exploratory Center Grants for hESC Research (NIGMS) Exploratory Center Grants for hESC Research (NIGMS) (Letter of intent 2/13/03; receipt date 3/13/03)(Letter of intent 2/13/03; receipt date 3/13/03)

Multi-investigator teams to conduct multidisciplinary Multi-investigator teams to conduct multidisciplinary research using hESCsresearch using hESCs

Infrastructure, growth and maintenance, biochemical/ Infrastructure, growth and maintenance, biochemical/ molecular markers for hESCs, unique properties of hESCs, molecular markers for hESCs, unique properties of hESCs, pilot studies leading to additional investigator-initiated pilot studies leading to additional investigator-initiated research grant applicationsresearch grant applications

P20 Exploratory Center Grant, leading to P50 applicationP20 Exploratory Center Grant, leading to P50 application

$2M in 2003, funding 2-3 P20 grant applications for up to 3 $2M in 2003, funding 2-3 P20 grant applications for up to 3 years at $500,000 direct/yearyears at $500,000 direct/year

Additional PAs/RFAsAdditional PAs/RFAs

Innovative Concepts and Approaches to Developing Innovative Concepts and Approaches to Developing Functional Tissues and Organs for Heart, Vascular, Functional Tissues and Organs for Heart, Vascular, Lung, and Blood Applications (R21) (NHLBI)Lung, and Blood Applications (R21) (NHLBI)

Plasticity of Human Stem Cells in the Nervous System Plasticity of Human Stem Cells in the Nervous System (R01) (NINDS, NIA, NIMH, NHLBI)(R01) (NINDS, NIA, NIMH, NHLBI)

Basic and Applied Stem Cell Research for Arthritis and Basic and Applied Stem Cell Research for Arthritis and Musculoskeletal Diseases (RO1) (NIAMS)Musculoskeletal Diseases (RO1) (NIAMS)

Stem Cells in Development/Repair of Orofacial Stem Cells in Development/Repair of Orofacial Structures (NIDCR)Structures (NIDCR)

Additional PAs/RFAsAdditional PAs/RFAs

Basic Research on Mesenchymal Cell Biology (NIA, Basic Research on Mesenchymal Cell Biology (NIA, NHLBI) NHLBI)

Comprehensive Programs in Beta Cell Biology (NIDDK)Comprehensive Programs in Beta Cell Biology (NIDDK)

Hematopoietic Cell Lineage Genome Anatomy (NIDDK)Hematopoietic Cell Lineage Genome Anatomy (NIDDK)

Cellular Repair Studies of the Auditory and Vestibular Cellular Repair Studies of the Auditory and Vestibular System (NIDCD)System (NIDCD)

Research on Stem Cell Biology and Cell-based Research on Stem Cell Biology and Cell-based Therapies for Heart, Lung, Blood, and Sleep Disorders Therapies for Heart, Lung, Blood, and Sleep Disorders (NHLBI)(NHLBI)

Stem Cell Research for Alcohol-related Disorders Stem Cell Research for Alcohol-related Disorders (NIAAA)(NIAAA)

NIH NIH Intramural ResearchIntramural Research

Nine laboratories at NIH are currently Nine laboratories at NIH are currently using hESC in their researchusing hESC in their research

Expanding interest as cell line availability Expanding interest as cell line availability becomes more straightforwardbecomes more straightforward

Creation of a stem cell characterization Creation of a stem cell characterization unit within Intramural Research Program unit within Intramural Research Program at NIHat NIH

Human ES Cell Research Human ES Cell Research SymposiumSymposium

Showcased research conducted and Showcased research conducted and supported by NIH on June 13, 2003supported by NIH on June 13, 2003

Podium presentations and posters Podium presentations and posters

Workshops on topics of interest (cell Workshops on topics of interest (cell culture, policy, intellectual property)culture, policy, intellectual property)

Immediately after the GM Stem Cell Immediately after the GM Stem Cell Symposium on June 10-11, 2003Symposium on June 10-11, 2003

Highlights of Human ES Cell Highlights of Human ES Cell Research ProgressResearch Progress

Neural differentiation—protocol described Neural differentiation—protocol described to generate dopamine secreting neurons to generate dopamine secreting neurons similar the midbrain neurons lost in similar the midbrain neurons lost in Parkinson’s diseaseParkinson’s disease

Pluripotency/Self Renewal—discovery of Pluripotency/Self Renewal—discovery of Nanog, a transcription factor that serves Nanog, a transcription factor that serves as a master regulator of pluripotent and as a master regulator of pluripotent and self renewing state of human ES cellsself renewing state of human ES cells

Highlights of Human Es Cell Highlights of Human Es Cell Research (cont.)Research (cont.)

Hematopoietic differentiation—culture Hematopoietic differentiation—culture conditions being defined that promote conditions being defined that promote specialization of human ES cells into blood specialization of human ES cells into blood forming cellsforming cellsCardiac myocyte differentiation—Cardiac myocyte differentiation—functional characterization of atrial, functional characterization of atrial, ventricular, and nodal cardiac myocytes ventricular, and nodal cardiac myocytes differentiated from human ES cells in differentiated from human ES cells in cultureculture

Research Advances using Other Research Advances using Other Types of Stem CellsTypes of Stem Cells

Neuronal stem cells—discovery and Neuronal stem cells—discovery and characterization of a source of self-characterization of a source of self-renewing neural progenitor cells in adult renewing neural progenitor cells in adult brain white matterbrain white matter

Dental pulp stem cells—discovery of a Dental pulp stem cells—discovery of a pluripotent population of stem cells in pluripotent population of stem cells in dental pulp of deciduous teeth which can dental pulp of deciduous teeth which can be cultured and dividesbe cultured and divides

Research Advances using Other Research Advances using Other Types of Stem Cells (cont.)Types of Stem Cells (cont.)

Hematopoietic stem cells—discovery that Wnt Hematopoietic stem cells—discovery that Wnt pathway can promote self renewal of pathway can promote self renewal of hematopoietic stem cells in culturehematopoietic stem cells in cultureMultipotent Adult Progenitor Cells (MAPC)—Multipotent Adult Progenitor Cells (MAPC)—bone marrow mesenchymal stem cell with bone marrow mesenchymal stem cell with capacity to self renew and become many capacity to self renew and become many different specialized cellsdifferent specialized cellsUmbilical cord stem cells—research to define Umbilical cord stem cells—research to define culture conditions that promotes expansion of culture conditions that promotes expansion of cells obtained from a single unit in culturecells obtained from a single unit in culture

Research advances (cont.)Research advances (cont.)

Human EG cells—in a rat model for ALS, Human EG cells—in a rat model for ALS, scientists restored movement by scientists restored movement by transplanting EG cells, which secrete transplanting EG cells, which secrete factors that promote survival of factors that promote survival of endogenous neuronsendogenous neuronsMuscle stem cells (satellite cells)—Muscle stem cells (satellite cells)—scientists determined that the Wnt scientists determined that the Wnt signaling pathway activates muscle signaling pathway activates muscle formationformation

NIH Supports Research on Many NIH Supports Research on Many Types of Stem CellsTypes of Stem Cells

Early phase of research—breakthroughs Early phase of research—breakthroughs with clinical relevance might emerge from with clinical relevance might emerge from research on many types of stem cellsresearch on many types of stem cells

FY2002 investment in human adult stem FY2002 investment in human adult stem cell research--$170,745,000cell research--$170,745,000

FY2002 investment in human embryonic FY2002 investment in human embryonic stem cell research--$10,689,000stem cell research--$10,689,000

Promote growth in both areas in the futurePromote growth in both areas in the future

On the Research HorizonOn the Research Horizon

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

Horizon (cont.)Horizon (cont.)

Determine the factors/conditions critical for Determine the factors/conditions critical for long-term survival and function of long-term survival and function of transplanted cells in a hosttransplanted cells in a host

Understand control of cell division—Understand control of cell division—essential to expand cells before essential to expand cells before specialization, but must be tightly specialization, but must be tightly regulated after transplantation for therapyregulated after transplantation for therapy

NIH Stem Cell Web SitesNIH Stem Cell Web Sites

Stem Cell InformationStem Cell Information– stemcells.nih.govstemcells.nih.gov

Human Embryonic Stem Cell RegistryHuman Embryonic Stem Cell Registry– escr.nih.goescr.nih.go