Autologous CD34+ Cell Therapy for Therapeutic Angiogenesis in Advanced PAD

自体 CD34 细胞疗法用于治疗晚期 PAD 的血管生成

• 批准号: 7484974
• 负责人: DOUGLAS W LOSORDO
• 金额: $ 53万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7484974
• 关键词: Adverse effects; Age; Alternative Therapies; Amputation; Anatomy; Autologous; Blood; Blood Vessels; Bone Marrow; Bone Marrow Cells; Bypass; CD34 gene; Catheters; Cell Therapy; Cells; Clinical; Clinical Data; Clinical Protocols; Clinical Research; Clinical Trials; Data; Data Set; Disabled Persons; Disease; Distal; End Point; Endothelial Cells; Equilibrium; Exhibits; Failure; Goals; Healed; Human; Injection of therapeutic agent; Intermittent Claudication; Intervention; Intramuscular Injections; Investigation; Ischemia; Laboratories; Lead; Limb structure; Lower Extremity; Mechanics; Medical; Numbers; Operative Surgical Procedures; Pain; Patients; Perfusion; Peripheral arterial disease; Phase; Phase II Clinical Trials; Physiology; Pilot Projects; Population; Prevalence; Process; Protocols documentation; Purpose; Randomized Controlled Clinical Trials; Recombinant Proteins; Research Personnel; Rest; Safety; Seminal; Series; Signal Transduction; Signs and Symptoms; Site; Stem cells; Symptoms; Techniques; Testing; Therapeutic Agents; Tissues; Translating; Ulcer; Walking; Work; artery occlusion; base; claudication; concept; cytokine; design; gene therapy; healing; improved; insight; neovascularization; novel therapeutics; pre-clinical; preclinical study; therapeutic angiogenesis

DESCRIPTION (provided by applicant):  The age-adjusted prevalence of peripheral arterial disease (PAD) in the U.S. population has been estimated to approach 12%. The clinical consequences of occlusive PAD include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of certain patients with PAD. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and/or healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients, for many of whom amputation represents the only hope for alleviation of symptoms. The ultimate failure of medical treatment and mechanical revascularization in significant numbers of patients has led to attempts to develop alternative therapies for ischemic disease. These strategies include administration of angiogenic cytokines, either as recombinant protein or as gene therapy, and more recently, to investigations of cell therapy. The concept that new blood vessel formation could be augmented by administering bone marrow cells or circulating endothelial progenitor cells (EPCs) is based upon work performed in our laboratory and others in the past 7 years. The purpose of this pilot clinical protocol is to investigate the efficacy and safety of intramuscular injection of autologously derived EPCs in patients with PAD as a means of augmenting blood vessel formation and perfusion. The rationale for this human protocol is based upon preclinical studies performed in our laboratory and detailed in this application. The completion of the proposed studies will provide data regarding the safety and efficacy of EPC therapy necessary for the design of larger randomized trials and will also provide valuable insights regarding treatment of ischemic disease with a cell based approach.

描述（由申请人提供）：据估计，美国人群中周围动脉疾病（PAD）的年龄调整后的患病率估计接近12％。闭塞垫的临床后果包括步行疼痛（lau不平），静止疼痛以及远端四肢组织完整性的丧失；后者最终可能导致下肢一部分的截肢。手术旁路技术和经皮基于导管的干预措施可用于成功地将某些PAD患者的肢体血运重建。但是，在许多患者中，动脉闭塞的解剖学范围和分布太严重，无法缓解缺血性溃疡的疼痛和/或治愈。没有有效的医疗疗法可用于治疗此类患者，其中许多截肢代表了减轻症状的唯一希望。医疗治疗和大量患者的机械血运重建的最终失败导致试图开发缺血性疾病的替代疗法。这些策略包括给予血管生成细胞因子，即重组蛋白或作为基因疗法，以及最近对细胞疗法的研究。可以通过施用骨髓细胞或循环内皮祖细胞（EPC）来增强新血管形成的概念是基于过去7年中在我们的实验室中所做的工作。该试验临床方案的目的是研究肌肉内注射自体衍生的EPC在PAD患者中的疗效和安全性，以增加血管形成和灌注。该人类协议的基本原理是基于在我们的实验室中进行的临床前研究，并在本应用中详细介绍。拟议的研究的完成将提供有关设计大型随机试验所需的EPC治疗的安全性和功效的数据，并将提供有关细胞基础方法治疗缺血性疾病的宝贵见解。