The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells

使用促红细胞生成素重新编程口腔和颅面干细胞

• 批准号: 7838174
• 负责人: DAVID H. KOHN
• 金额: $ 48.59万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7838174
• 关键词: Achievement; Acute; Address; Adenoviruses; Adult; Affect; Animals; Apoptosis; Area; Beds; Biology; Biomedical Engineering; Blood; Bone Development; Bone Marrow; Bone Regeneration; Cancer Patient; Cell Culture Techniques; Cell Separation; Cell Therapy; Cell Transplants; Cell surface; Cells; Cephalic; Chronic; Cicatrix; Clinical; Coupling; Data; Defect; Disease; Elements; Erythropoietin; Exclusion; Face; Fibrosis; Fracture Healing; Healed; Hematopoiesis; Hematopoietic System; Hematopoietic stem cells; Hemorrhage; Human; In Vitro; Inflammation; Marrow; Mesenchymal; Mesenchymal Stem Cells; Modality; Modeling; Molecular; Natural regeneration; Occupations; Operative Surgical Procedures; Oral; Oral cavity; Osteogenesis; Pathway interactions; Phenotype; Physiological; Positioning Attribute; Process; Production; Radiation Toxicity; Radiation therapy; Reconstructive Surgical Procedures; Research Personnel; Science; Somatic Cell; Stem cells; Stromal Cells; Therapeutic; Tissues; Transplantation; Trauma; Vascular blood supply; Wound Healing; base; bone morphogenetic protein 2; bone morphogenetic protein 6; cell type; craniofacial; craniofacial complex; gene therapy; healing; human tissue; improved; in vivo; novel strategies; oral tissue; osteoblast differentiation; prospective; receptor; regenerative; regenerative therapy; repaired; scaffold; skeletal; stem cell population; tissue regeneration; translational study; vector; wound

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.

描述（由申请人提供）：使用促红细胞生成素在口腔和颅面干细胞中使用。该项目直接解决了挑战区域（14） - 茎细胞，特别是14-DE-101*对口腔和颅面组织的细胞重编程，在这些细胞中，我们开发了一种新型的方法，用于使用基于细胞的治疗和恢复疾病的细胞治疗和恢复细胞治疗的细胞治疗或依赖病态或创造性的细胞治疗方法，以对口腔和颅面复合物进行部分重编程。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）种群，在体内和体外都保持其多条形潜力。最重要的是，我们可以使用细胞表面标记来分离MSC，从而使我们能够前瞻性地隔离细胞而无需培养。这使我们与间充质生物学领域的其他人区分开来。在该项目中，我们将合并我们的两项研究，以确定EPO是否可以部分重新编程成人MSC，用于重新造成非治疗伤口的再生，该提案将是我们范式的关键转变和弹簧板用于控制组织再生的生物工程，我们相信我们认为最终将在人类组织的广泛范围内使用。我们的总体假设是，红细胞生成素（EPO）可用于重新编程骨骼前体和可用于骨骼修复的间质干细胞。我们的方法是确定是否可以使用EPO重新编程骨髓基质细胞以及后来的MSC，以促进非锁骨修复和受照射的临界大小的骨缺陷。目的1。确定BMSC在多大程度上重新编程以表达EPO能够再生受放射治疗损害的关键大小的颅面缺陷。目标2：确定EPO是否可以部分重新编程基于细胞的疗法的MSC，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，并加快科学的步伐和成就。该项目的完成是可行的两年，然后我们的小组将在口腔和颅面再生方面提出并完成更多机械和转化研究。 2红细胞生成素可用于重新编程骨骼前体和可用于骨骼修复的间充质干细胞。