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: 7171598
• 负责人: DOUGLAS W LOSORDO
• 金额: $ 52.69万
• 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 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171598
• 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）：美国人口中外周动脉疾病 (PAD) 的年龄调整患病率估计接近 12%。闭塞性 PAD 的临床后果包括行走时疼痛（跛行）、休息时疼痛以及远端肢体组织完整性丧失；后者可能最终导致部分下肢截肢。外科搭桥技术和基于经皮导管的干预措施可用于成功地对某些 PAD 患者的四肢进行血运重建。然而，在许多患者中，动脉闭塞的解剖范围和分布过于严重而无法缓解疼痛和/或治愈缺血性溃疡。目前尚无有效的药物疗法可用于治疗此类患者，对许多患者来说，截肢是缓解症状的唯一希望。大量患者的药物治疗和机械血运重建最终失败，导致人们尝试开发缺血性疾病的替代疗法。这些策略包括施用血管生成细胞因子，作为重组蛋白或基因疗法，以及最近的细胞疗法研究。通过给予骨髓细胞或循环内皮祖细胞 (EPC) 可以增强新血管形成的概念是基于我们实验室和其他实验室在过去 7 年中所做的工作。该试点临床方案的目的是研究 PAD 患者肌内注射自体 EPC 作为增强血管形成和灌注的手段的有效性和安全性。该人体方案的基本原理基于我们实验室进行的临床前研究，并在本申请中详细说明。拟议研究的完成将为设计更大规模的随机试验提供必要的有关 EPC 疗法的安全性和有效性的数据，还将提供关于使用基于细胞的方法治疗缺血性疾病的宝贵见解。