Cardiovascular Regenerative Medicine

心血管再生医学

• 批准号: 8464219
• 负责人: Douglas E Vaughan
• 金额: $ 199.86万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-07 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464219
• 关键词: Aging; Amputation; Animals; Autologous; Belief; Biology; CD34 gene; Cardiovascular Diseases; Cardiovascular system; Cell Separation; Cell Therapy; Cell physiology; Cells; Chest Pain; Chronic; Clinical Trials; Collaborations; Data; Defect; Diabetes Mellitus; Disease; Doctor of Medicine; Doctor of Philosophy; Environment; Epigenetic Process; Exercise Tolerance; Fibrosis; Functional disorder; Goals; Histology; Human; Individual; Ischemia; Knowledge; Limb structure; Methods; Mitochondria; Myocardial; Operative Surgical Procedures; Outcome; Patients; Peptides; Plasminogen Activator Inhibitor 1; Principal Investigator; Recruitment Activity; Refractory; Regenerative Medicine; Role; Safety; Stem cells; Therapeutic; Therapeutic Uses; base; design; improved; interest; member; molecular imaging; nanomaterials; novel; phase 3 study; programs; repaired

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.)

描述（由申请人提供）： 项目负责人十年来致力于开发基于内皮祖细胞的疗法而产生的最新数据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。具体而言，最近的两项人体临床试验均得出证据表明，自体人类 CD34+ 细胞可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着减轻，运动耐量提高，而严重肢体缺血患者的截肢率降低。虽然我们承认基于祖细胞的疗法的 III 期研究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现有证据足以证明通过利用我们的研究成果来增强其疗效的努力是合理的。了解其生物学并进一步探索可能增强其安全性和治疗效用的机制。该 PPG 的总体目标是推进内皮祖细胞在心血管疾病治疗中的应用。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，并探索基于纳米材料的新颖方法来增强其治疗应用，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（Douglas W. Losordo，医学博士和 Samuel Stupp 博士，Co-I） 项目 2：PAI-1 在心血管修复和纤维化中的作用（Douglas E. Vaughan，医学博士） ，PI）项目 3：糖尿病和衰老中 EPC 线粒体缺陷的表征（Hossein Ardehali， M.D.、Ph.D.、PI) 项目 4：内皮祖细胞对心肌发生的表观遗传调节（Raj Kishore，Ph.D.、PI） 核心 A：小动物手术和组织学（Tsutomu Kume，Ph.D.、PI）核心 B：高级分子成像（Tom Meade，博士，PI） 核心 C：FACS 分析和细胞分选（Harris Perlman，博士、研究员）核心 D；行政核心（Douglas Losordo，医学博士，PI） 项目 1：肽两亲物增强祖细胞疗法（Losordo，Douglas W.）