Autologous CD34+ Cell Therapy for Therapeutic Angiogenesis in Advanced PAD

描述（由申请人提供）：经年龄调整的外周动脉疾病（PAD）在美国人群中的患病率估计接近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；后者可能最终导致部分下肢截肢。外科旁路技术和经皮导管介入可用于某些PAD患者的肢体血运重建。然而，在许多患者中，动脉闭塞的解剖范围和分布太严重，无法缓解疼痛和/或愈合缺血性溃疡。没有有效的药物治疗可用于治疗这些病人，对其中许多人来说，截肢是减轻症状的唯一希望。大量患者的医疗和机械血运重建术最终失败，导致人们试图开发缺血性疾病的替代疗法。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还是作为基因治疗，以及最近的细胞治疗研究。新血管形成可以通过给予骨髓细胞或循环内皮祖细胞（EPCs）来增强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肌内注射自体来源的内皮祖细胞作为一种增强血管形成和灌注的手段在PAD患者中的有效性和安全性。这个人体协议的基本原理是基于在我们实验室进行的临床前研究，并在本应用程序中详细说明。拟议研究的完成将为EPC治疗的安全性和有效性提供数据，这对于设计更大的随机试验是必要的，也将为基于细胞的方法治疗缺血性疾病提供有价值的见解。

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.