The laboratory has an active program for ex vivo culture and expansion of hematopoietic stem cells from adult marrow, G-CSF mobilized peripheral blood and umbilical cord blood for potential use for unrelated donor transplantation for treatment of leukemia, lymphoma and multiple myeloma, aplastic anemia and genetic disorders of the hematopoietic and immune system. By using combinations of cytokines (thrombopoietin, VEGF, cKit ligand, Flt3 ligand, IL-7) and morphogens (BMP's, Notch ligands) and modifying homeobox protein levels or STAT5 signaling pathways, we are expanding pluripotential stem cells as well as modifying differentiation along specific pathways to facilitate e.g platelet reconstitution, T lymphocyte recovery. We have developed gene therapy strategies in which human hematopoietic stem cells can be genetically modified by retroviral or lentiviral gene transduction. Such gene therapy may be of clinical value for treatment of genetic disease of the immune and blood cell forming systems.
