Autologous CD34+ Cell Therapy for Therapeutic Angiogenesis in Advanced PAD

描述（由申请人提供）：  据估计，美国人群中经年龄调整的外周动脉疾病（PAD）患病率接近12%。闭塞性PAD的临床后果包括行走疼痛（跛行）、休息时疼痛和远端肢体组织完整性丧失;后者可能最终导致下肢部分截肢。外科旁路技术和经皮导管介入可用于成功地实现某些PAD患者肢体的血运重建。然而，在许多患者中，动脉闭塞的解剖学范围和分布过于严重，无法缓解疼痛和/或愈合缺血性溃疡。没有有效的医学疗法可用于治疗这些患者，对其中许多人来说，截肢是减轻症状的唯一希望。大量患者的药物治疗和机械血运重建的最终失败导致了开发缺血性疾病替代疗法的尝试。这些策略包括血管生成细胞因子的管理，无论是作为重组蛋白或基因治疗，以及最近的细胞治疗的调查。通过给予骨髓细胞或循环内皮祖细胞（EPCs）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年中进行的工作。本试验性临床方案的目的是研究PAD患者肌内注射自体来源的EPCs作为增强血管形成和灌注的方法的有效性和安全性。该人体方案的依据是基于我们实验室进行的临床前研究，并在本申请中详述。拟议研究的完成将提供设计大型随机试验所需的EPC治疗安全性和有效性的数据，并将提供有关以细胞为基础的方法治疗缺血性疾病的有价值的见解。

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.