J. Victor Garcia-Martinez, Ph. D.
Professor
Division of Infectious Diseases

Dallas, TX 75390-9113
Phone (214) 648-9970
Fax (214) 648-0231
Email victor.garcia@utsouthwestern.edu

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 HSCs are readily evaluated by transplantation in mice, analysis in humans is quite difficult.

Progress in the characterization of human HSC has relied, for the most part, on in vitro assays such as clonogenic assays (CFCs) and of long-term cultures (LTC-IC). Interest in human 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 human HSC. These models are based on the fact that human hematopoietic cells from fetal liver, bone marrow, umbilical cord or peripheral blood (after mobilization) can repopulate the bone marrow of severe combined immune deficient (SCID) mice.

Our objective is to use two different but complementary xenograft models to evaluate the in vivo repopulating potential and the suitability for gene transfer of HSC isolated from HIV infected individuals. Since ultimately this is the only source available for cells suitable genetic manipulations, this analysis represents an indispensable and important component of future gene therapy protocols. Our specific goals 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 infected individuals; and 3) To characterize the primitive hematopoietic stem cell compartment in HIV-1 infected individuals.