: Hematopoietic stem cells (HSC) play a central role in the production of all hematopoietic lineages. HSC are functionally defined as having two important characteristics: self-renewal and the capacity to differentiate into all mature hematopoietic lineages. These two characteristics are in sharp contrast to those of mature cells that have limited proliferation and differentiation potential and lack self-renewal properties. In order to maintain a functional hematopoietic system, a population of HSC must be able to regenerate the entire hematopoietic repertoire on a regular basis. Whereas HSC are readily evaluated by transplantation in mice, analysis in humans is quite difficult. Progress in the characterization of HSC has relied, for the most part, on in vitro assays such clonogenic assays (CFCs) and of long-term cultures (LTC-IC). Interest in HSC is widespread because of their many possible clinical applications including transplantation, purging of tumor cells, and gene therapy. Recently, the use of xenografts has facilitated the analysis of the HSC. These models are based on the fact that human hematopoietic cells from fetal liver, bone marrow, umbilical core or peripheral blood (after mobilization) can repopulate the bone marrow of severe combined immune deficient (SCID) mice. In this competitive renewal application in which the investigators propose to use two different but complementary xenograft models to evaluate the in vivo repopulating potential and the suitability for gene transfer of HSC from HIV infected individuals. Since ultimately this is the only source available for cells of future gene therapy protocols.
The specific aims of this proposal are: 1) To determine the quantitative in vivo repopulating potential of hematopoietic stem cells from HIV-1 infected individuals; 2) To determine the in vivo lymphopoietic capacity of T-cell progenitors from HIV-1 individuals; and 3) To characterize the primitive hematopoietic stem cell compartment in HIV-1 infected individuals.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Special Emphasis Panel (ZRG1-AARR-1 (11))
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Howcroft, Thomas K
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University of Texas Sw Medical Center Dallas
Internal Medicine/Medicine
Schools of Medicine
United States
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