HEMATOPOIETIC RECONSTITUTION USING ISOLATED PROGENITOR CELL SUBPOPULATIONS

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The goal of the studies in this project is to determine the ability of specific subsets of marrow-derived progenitor cells to reconstitute lymphohemaotpoiesis in vivo in baboons. To date we have obtained the following important results (1) The CD34 antigen is expressed by marrow cells that reconstitute stable long-term lymphopoiesis and myelopoiesis after transplantation of lethally irradiated baboons. Three animals that were transplanted with purified allogeneic CD34+ marrow cells devoid of mature and immature T and B lymphocytes remain alive and healthy as stable hematopoietic chimeras more than 1100, 1020, and 640 days after transplantation. (2) Transplantation of these purified CD34+ cells between HLA matched animals has produced no detectable graft vs. host disease. (3) CD34+ marrow cells expressing the highest levels of the class II antigen HLA-DR engraft lethally irradiated animals more rapidly than does the subset of CD34+ marrow cells expressing low or undetectable levels of HLA-DR. (4) Both the Lineage positive and Lineage negative subpopulations of CD34+ marrow cells can engraft lethally irradiated baboons, and the Lineage negative subpopulation can reconstitute lymphohematopoiesis. (5) The Lineage negative, HLA-DR negative, CD34+ marrow cells can contribute progeny to both the myeloid and lymphoid lineages following transplantation, consistent with possible stem cell function; however, by themselves they are insufficient for rescuing lethally irradiated animals. Studies to further define the specific role of subsets of CD34+ marrow and peripheral blood cells in marrow reconstitution after transplantation are in progress. Likewise, studies are under way to introduce clonal markers into subpopulations of marrow repopulating CD34+ stem cells, in order to establish the capacity of individual cells to lymphohematopoietic stem cells in vivo.