This Phase I project will examine the effects of cytokines on hematopoietic progenitor cells (HPCs) using a novel three-dimensional biomaterial, Cellfoam TM . Preliminary work has shown that Cellfoam enables the culture of CD34+/CD38- HPCs and the maintenance of their multipotent and immature phenotype for periods of up to three weeks in the absence of supplemented cytokines. This unique capability will be exploited in Phase 1 to examine the effects of specific cytokines (IL-3, IL-6 and stem cell factor), individually and in groups, on HPC biology. Operating from the hypothesis that the addition of cytokines to cultures of HPCs in vitro will affect HPC survival and multipotency, this project will specifically focus on measuring the survival, phenotype and multipotency of HPCs cultured in Cellfoam for periods of three days to six weeks in the presence and absence of supplemented cytokines. This will allow a direct determination of the effects of selected cytokines on HPC biology in an environment that does not have an absolute requirement for cytokines in long-term HPC culturing. The findings of the Phase 1 research will be instrumental in the Phase Il development of Cellfoam systems enabling the maintenance and manipulation of stem cells over extended periods for clinical and research uses. PROPOSED COMMERCIAL APPLICATION: The proposed research will aid in the development of Cellfoam systems capable of manipulating hematopoietic stem cells using cytokines. Development of such devices would enable characterization of the effects of cytokines on HPC pluripotency and viability. Such devices ultimately will enable stem cell manipulation with cytokines, for instance in areas of basic science and clinical medicine such as blood cell production, stem cell analysis, bone marrow transplantation, transfusion medicine and gene therapy.
Thesaurus Terms:biomaterial development /preparation, bioreactor, biotechnology, cytokine, hematopoietic stem cell, tantalum, tissue /cell culture CD34 molecule, fibronectinNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)