The goal of this Phase I proposal is to develop chemically defined reagents that support hematopoietic stem cell proliferation and differentiation. Such reagents would be valuable in hematological research especially for bone marrow transplantation, gene therapy, and ex-vivo purging. Preliminary evidence indicates that it is feasible to replace the ill-defined and uncharacterized components with defined chemicals. A hall mark in the progress of hematological research has been the development of serum-free reagents. The serum-free reagents are a dramatic improvement over serum containing reagents but still contain ill-defined components as BSA. Replacement of these ill-defined components would be of inestimable importance especially in the development of U.S. pharmaceutical grade reagents. Typically these reagents have required the presence of human blood products, by-passing such components would eliminate the problems associated with blood procurement from human volunteers (hepatitis, HIV, etc.) along with the time and material involved. The Phase II effort will continue the development and optimization of chemically defined reagents for bone marrow expansion and their evaluation of use in bone marrow transplantation, gene therapy and ex vivo purging.
