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TITLE Regulated Expansion of Lympho-hematopoietic Stem and Progenitor Cells from Human Embryonic Stem Cells (hESC) ABSTRACT The clinical potential of human embryonic stem cells (hESC) for transplantation will be realized only when we can develop methods to control the process of tissue differentiation far more efficiently than is currently the case. From over 40 years of experience with adult stem cells, it is recognized that the growth of transplanted bone marrow is generated from the hematopoietic (blood-forming) stem and progenitor cells present in the graft. Mature, differentiated cells that accompany the stem cells disappear rapidly after transplantation as they lack the ability to self renew. It is thus essential when designing clinical approaches that use tissue derived from hESC, to specifically target the production of stem and progenitors that will survive, proliferate and differentiate after transplantation. This proposal addresses three fundamental questions for the entire hESC field 1.Do hESC differentiate through the same pathways that exist in adult tissues, 2.How do the conditions in which hESC are initially derived from blastocysts affect their subsequent potential for generating tissue specific stem and progenitor cells, and 3.How can hESC differentiation be regulated to provide large numbers of tissue specific stem and progenitor cells able to engraft and differentiate long term? Studies of hematopoiesis in mice have provided the conceptual basis for the entire field of stem cell biology. However, fundamental biological and technical differences exist in both hematopoietic and embryonic stem cell biology between the murine and human species. Our group has chosen over the past 15 years to focus on the study of human hematopoietic stem cells and lymphoid (immune system) progenitors, more recently bringing these concepts and tools to study hematopoietic differentiation from hESC. In brief, our aims in this proposal are: 1. To understand the pathways along which the blood and immune system are generated from hESC, 2. To assess if the methods by which hESC are derived affect their capacity for hematopoiesis, and 3. To develop the means to expand hematopoietic stem cells derived from hESC. I believe that there are two broad reasons why these studies are important. First, as a pediatric bone marrow transplant physician, I am keenly aware that profound clinical problems remain for my patients. Matched stem cells from he
PI Gay Crooks INSTITUTE Childrens Hospital Los Angeles STATE California AMOUNT $2,551,090.00 AWARD DATE 2007 March GRANT TYPE Comprehensive