P5: DIRECTED STEM CELL DIFFERENTIATION - HUMAN APPLICATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are two specific aims to this project. Aim one involves human cell stem/progenitor cells. We will be performing parallel experiments based on our murine work. We have found that it is possible to "program" the stem/progenitor cells to make specific progeny by giving them a signal. This signal is composed of cytokines. We have found that at certain points in cell cycle, the stem/progenitor cells are more sensitive and open to receive these signals. What makes this unique is that we are able to direct these cells before they begin dividing, which means that we do not take away any of their full growth potential or stem cell properties. It is hoped that with more work, we are able to "program" these cells to make a specific lineage and transplant these cells into a patient that is deficient in that specific lineage. The potential application is broad and this work could end up changing the way we perform bone marrow transplantation. In addition, this work has the potential to make bone marrow transplantation safer with improved survival as some transplants we perform still has an upfront mortality approaching 50%. Aim two involves using the results of aim one and testing the "programmed" cell population in an in vivo model. We will determine the in vivo functional capacity of directed human marrow populations derived from aim one with a transplant model. Overall, the results from this project will be crucial to the development of successful bioprocessing techniques. The techniques can eventually lead to improvement in bone marrow transplantation outcomes.