Cardiovascular Regenerative Medicine

描述(由申请人提供)： 最近的数据是PI计划十年来努力开发基于内皮祖细胞的疗法的结果，为自体祖细胞用于治疗心肌和肢体缺血的安全性和有效性提供了证据。具体地说，最近的两项人类临床试验都证明，自体人类CD34+细胞可以改善慢性难治性缺血患者的预后：顽固性心绞痛患者的胸痛显著减轻，运动耐量提高，而严重肢体缺血患者的截肢率降低。虽然我们承认在第三阶段研究中祖细胞疗法的最终证据即将到来，但我们相信基于细胞疗法的生物活性和潜在治疗效用的现有证据足够充分，足以证明通过利用我们对其生物学的知识和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。该PPG的首要目标是促进内皮祖细胞在心血管疾病治疗中的治疗应用。该计划将通过四个单独的项目来实现这一目标，这些项目研究祖细胞命运、功能和功能障碍的某些机制，探索基于纳米材料的新方法，以增强其治疗应用，并利用将支持每个项目的战略性设计的核心。项目1：使用生物活性多肽两亲性增强祖细胞功能(Douglas W.Losordo，M.D.和Samuel Stupp Ph.D.，Co-I)项目2：PAI-1在心血管修复和纤维化中的作用(Douglas E.Vaughan，M.D.，Pi)项目3：糖尿病和老龄化中内皮祖细胞线粒体缺陷的特征(Hossein Ardehali，M.D.，Ph.D.，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：小动物手术和组织学(Tsutomu Kume，Ph.D.，Pi)。PI)核心B：高级分子成像(Tom Meade，Ph.D.，PI)核心C：FACS分析和细胞分类(Harris Perlman，Ph.D.，PI)核心D；管理核心(Douglas Losordo，M.D.，PI) 项目1：增加祖细胞疗法的两亲多肽(Losordo，Douglas 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.)