Cardiovascular Regenerative Medicine

描述（由申请人提供）： 最近的数据，作为PI计划开发基于内皮祖细胞的治疗剂的十年努力的结果，为自体祖细胞治疗心肌和肢体缺血的安全性和有效性提供了证据。特别是最近的两项人体临床试验都证明了自体人CD 34+细胞可以改善慢性难治性缺血患者的预后：顽固性心绞痛患者胸痛明显减轻，运动耐量提高，而严重肢体缺血患者截肢率降低。虽然我们承认III期研究中基于祖细胞的疗法的最终证据即将到来，但我们相信，基于细胞的疗法的生物活性和潜在治疗效用的可用证据足以证明通过利用我们关于其生物学的知识并进一步探索可能增强其安全性和治疗效用的机制来增强其疗效的努力是合理的。本PPG的首要目标是推进内皮祖细胞在心血管疾病治疗中的治疗用途。这一目标将在该计划中通过四个单独的项目来实现，这些项目将调查祖细胞命运，功能和功能障碍的某些机制，并探索基于纳米材料的新方法以增强其治疗应用，并利用战略设计的核心来支持每个项目。项目1：使用生物活性肽两亲物增强祖细胞功能（道格拉斯W. Losordo，医学博士和塞缪尔·斯图普博士Co-I）项目2：派-1在心血管修复和纤维化中的作用（道格拉斯E.沃恩，医学博士，PI）项目3：糖尿病和衰老中EPC中线粒体缺陷的表征（Hossein Ardehali，M.D.，博士，PI）项目4：用于心肌发生的内皮祖细胞的表观遗传调节（Raj Kishore，Ph.D.，PI）核心A：小动物外科和组织学（Tsutomu Kume，Ph.D.，PI）核心B：高级分子成像（Tom米德，博士，PI）核心C：FACS分析和细胞分选（Harris Perlman，Ph.D.，PI）核心D;管理核心（道格拉斯Losordo，医学博士，PI） 项目1： 增强祖细胞治疗的肽两亲物（Losordo，道格拉斯W.）

DESCRIPTION (provided by applicant): Recent data, generated as the result of a decade long effort by the Program PI to develop endothelial progenitor cell based therapeutics, provides evidence for the safety and efficacy of autologous progenitor cells for treatment of myocardial and limb ischemia. Specifically two recent human clinical trials have both yielded evidence that autologous human CD34+ cells improve outcome in patients with chronic, refractory ischemia: patients with intractable angina had significant reductions in chest pain and improved exercise tolerance, while patients with critical limb ischemia had reduced amputation rates. While we acknowledge that the final proof of progenitor cell based therapies in phase III studies is forthcoming, it is our belief that the available evidence for bioactivity and potential therapeutic utility of cell based therapy is substantial enough to justify efforts to augment their efficacy by exploiting our knowledge about their biology and further exploring mechanisms that may enhance their safety and therapeutic utility. The overarching goal of this PPG is to advance the therapeutic use of endothelial progenitor cells for the treatment of cardiovascular diseases. This objective will be achieved in the Program by four individual Projects that investigate certain mechanisms of progenitor cell fate, function and dysfunction, and explore novel, nanomaterial based methods to enhance their therapeutic application and by taking advantage of strategically designed Cores that will support each Project. Project 1: Enhancing Progenitor Cell Function using Bioactive Peptide Amphiphiles (Douglas W. Losordo, M.D. and Samuel Stupp Ph.D., Co-I) Project 2: Role of PAI-1 in Cardiovascular Repair and Fibrosis (Douglas E. Vaughan, M.D., PI) Project 3: Characterization of mitochondrial defects in EPCs in diabetes and aging (Hossein Ardehali, M.D., Ph.D., PI) Project 4: Epigenetic modulation of Endothelial Progenitor Cells for Cardiomyogenesis (Raj Kishore, Ph.D., PI) Core A: Small Animal Surgery and Histology (Tsutomu Kume, Ph.D., PI) Core B: Advanced Molecular Imaging (Tom Meade, Ph.D., PI) Core C: FACS Analysis and Cell Sorting (Harris Perlman, Ph.D., PI) Core D; Administrative Core (Douglas Losordo, M.D., PI) PROJECT 1: Peptide Amphiphiles to Augment Progenitor Cell Therapies (Losordo, Douglas W.)