Autologous CD34+ Cell Therapy for Therapeutic Angiogenesis in Advanced PAD

描述(申请人提供)：美国人口中经年龄调整的外周动脉疾病(PAD)患病率估计接近12%。闭塞垫的临床后果包括行走时的疼痛(跛行)、休息时的疼痛和四肢远端组织完整性的丧失；后者最终可能导致部分下肢截肢。外科旁路技术和基于经皮导管的介入可以成功地对某些PAD患者的肢体进行血管重建。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。对于这些患者，没有有效的治疗方法可用，对他们中的许多人来说，截肢是缓解症状的唯一希望。在相当数量的患者中，医疗和机械血管重建术的最终失败导致了对缺血性疾病的替代疗法的尝试。这些策略包括给予血管生成细胞因子，作为重组蛋白或基因治疗，以及最近用于细胞治疗的研究。通过注射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。这一试点临床方案的目的是研究在PAD患者肌肉内注射自体来源的EPC作为一种增加血管形成和灌流的方法的有效性和安全性。这一人类方案的基本原理是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。拟议研究的完成将提供有关EPC疗法的安全性和有效性的数据，这对于设计更大的随机试验是必要的，也将为以细胞为基础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.