P5: DIRECTED STEM CELL DIFFERENTIATION - HUMAN APPLICATION

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目有两个具体目标。目的一涉及人类细胞干/祖细胞。我们将在小鼠实验的基础上进行平行实验。我们已经发现，通过给干/祖细胞一个信号，可以对它们进行“编程”，使它们产生特定的后代。该信号由细胞因子组成。我们已经发现，在细胞周期的某些点，干/祖细胞更敏感，更开放地接收这些信号。这种方法的独特之处在于，我们能够在这些细胞开始分裂之前对其进行指导，这意味着我们不会剥夺它们的全部生长潜力或干细胞特性。希望通过更多的工作，我们能够“编程”这些细胞以产生特定的谱系，并将这些细胞移植到缺乏该特定谱系的患者体内。潜在的应用是广泛的，这项工作可能最终改变我们进行骨髓移植的方式。此外，这项工作有可能使骨髓移植更安全，提高生存率，因为我们进行的一些移植仍然有接近50%的前期死亡率。目标二涉及使用目标一的结果，并在体内模型中测试“编程”细胞群。 我们将用移植模型确定来自目标1的定向人骨髓群体的体内功能能力。 总的来说，该项目的结果将对成功的生物加工技术的发展至关重要。这些技术最终可以改善骨髓移植的结果。

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.