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TITLE Understanding hESC-based Hematopoiesis for Therapeutic Benefit ABSTRACT Hematopoietic stem cell transplantation is the treatment of choice for many hematologic malignancies, and it is used to treat an expanding number of congenital blood disorders. However, only ~30% of patients who can benefit from this treatment have a matched sibling that can serve as the ideal donor. While the national marrow donor program and umbilical cord blood programs provide unrelated donor cells to many patients lacking a sibling donor, a large percentage of patients remain without a suitable donor, leaving them with suboptimal therapeutic options. This problem is more severe in certain ethnic populations, including people of Latino and Asian descent, groups that constitute a large part of Californias population. New sources of therapeutic hematopoietic stem cells are therefore needed. Human embryonic stem cells, with their unlimited self-renewal capacity and their ability to generate all human cell types, provide a novel and exciting opportunity to obtain hematopoietic stem cells, thereby filling a critical therapeutic void. However, many hurdles remain before this vision can be realized, including the identification of more optimal human embryonic stem cell lines and better methods to direct the development of specific cell types from embryonic stem cells. This proposal seeks to shed new insight into how we might better control and direct the development of human embryonic stem cells into therapeutically useful hematopoietic stem cells that can be used for transplantation. Our effort focuses on understanding how a specific class of small RNAs, called microRNAs, regulates the differentiation of human embryonic stem cells into specific cell types. We aim to uncover the identity of microRNAs that are important for this process, which will serve as useful biomarkers, or guides,
PI Andrew Leavitt INSTITUTE University of California, San Francisco STATE California AMOUNT $2,566,700.00 AWARD DATE 2007 March GRANT TYPE Comprehensive