The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells

描述（由申请人提供）：使用促红细胞生成素重编程口腔和颅面干细胞。该项目直接解决了挑战领域(14)-干细胞，特别是14- de -101*口腔和颅面组织细胞重编程，我们开发了一种新的方法，使用促红细胞生成素（Epo）对口腔和颅面复合体的体细胞干细胞进行部分重编程，用于基于细胞的治疗，以治愈和恢复疾病或创伤后的这些组织。我们已经确定Epo能够在体外和体内诱导骨形成。我们还纯化了间充质干细胞（MSC）群体，使其在体内和体外都保持其多谱系潜力。最重要的是，我们可以使用细胞表面标记物分离MSCs，这使我们能够在没有培养的情况下分离细胞。这使我们在间充质生物学领域有别于其他人。在这个项目中，我们将结合我们的两项研究来确定Epo是否可以部分重编程成人间充质干细胞，以用于未愈合伤口的再生。这一建议将成为我们范式的关键转变，也是生物工程应用于控制组织再生的跳板，我们相信最终将广泛用于人体组织。我们的总体假设是，促红细胞生成素（Epo）可用于重编程骨骼前体和间充质干细胞，可用于骨骼修复。我们的方法将是确定Epo是否可以用于骨髓基质细胞重编程，以及后来的MSCs，以促进未愈合和辐照临界大小骨缺损的骨修复。目的1。确定骨髓间充质干细胞重编程表达EPO在多大程度上能够再生放射治疗损害的临界大小的颅面缺损。目的2：确定Epo是否可以部分重编程MSCs，用于基于细胞的治疗，以治愈和恢复疾病或创伤后的组织。该项目将促进创造就业机会，加快科学的步伐和成就。在两年的时间框架内完成该项目是可行的，我们的小组将处于一个突出的位置，提出并完成更多的口腔和颅面再生的机制和转化研究。促红细胞生成素可用于重编程骨骼前体和间充质干细胞，可用于骨骼修复。

DESCRIPTION (provided by applicant): The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells. This project directly addresses Challenge Area (14)-Stem Cells, specifically 14-DE-101* Reprogramming of Cells from Oral and Craniofacial Tissues in which we developed a novel approach for partial reprogramming of somatic stem cells of the oral and craniofacial complex using erythropoietin (Epo) for cell- based therapies to heal and restore these tissues following disease or trauma. We have identified that Epo is able to induce bone formation in vitro as well as in vivo. We have also purified mesenchymal stem cell (MSC) population that maintains its multi-lineage potential both in vivo and in vitro. Most importantly, we can isolate MSCs using cell surface markers that allows us to prospectively isolate the cells without culture. This sets us apart from others in the mesenchymal biology field. In this project we will combined our two studies to determine if Epo can partially reprogram adult MSCs to be used for regeneration of non-healing wounds This proposal will serve as a critical shift in our paradigm and a spring board for application of bioengineering to controlling tissue regeneration that we believe will ultimately be used in a broad range of human tissues. Our overall hypothesis is that erythropoietin (Epo) can be used to reprogram skeletal precursors and mesenchymal stem cells that can be harnessed for skeletal repair. Our approach will be to determine if Epo can be used to reprogram bone marrow stromal cells, and later MSCs, to facilitate osseous repair in nonhealing and irradiated critical sized boney defects. Aim 1. To determine the extent to which BMSCs reprogrammed to express EPO are capable of regenerating critical sized cranio-facial defects compromised by radiation therapy. Aim 2: To determine whether Epo can partially reprogram MSCs for cell-based therapies to heal and restore tissues following disease or trauma. This project will promote job creation, and accelerate the pace and achievement of science. The completion of the project is feasible in a two year timeframe and our group will then be in an outstanding position to propose and complete more mechanistic and translational studies in oral and craniofacial regeneration. 2 Erythropoietin can be used to reprogram skeletal precursors and mesenchymal stem cells that can be harnessed for skeletal repair.