Modulating the vascular response to limb ischemia: angiogenic and cell therapies.
Modulating the vascular response to limb ischemia: angiogenic and cell therapies.
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DOI：
10.1161/circresaha.115.303565
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发表时间：
2015-04-24
影响因子：
20.1
通讯作者：
Losordo DW
中科院分区：
文献类型：
--
作者：
Cooke JP;Losordo DW
据估计，美国人口中按年龄调整的外周动脉疾病患病率接近 12%。闭塞性外周动脉疾病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以成功地对某些患有外周动脉疾病的患者的肢体进行再灌注。然而，在许多患者中，动脉闭塞的解剖范围和分布过于严重，无法缓解疼痛和治愈缺血性溃疡。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手术血运重建最终失败，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，以及最近的干/祖细胞疗法的研究。本综述的目的是概述血管生成和干细胞疗法的临床前基础，回顾已完成的临床研究，总结经验教训，找出知识差距，并提出成功解决大量且不断增长的患者群体中未满足的医疗需求的方案。
The age-adjusted prevalence of peripheral arterial disease in the US population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease 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 successfully reperfuse the limbs of certain patients with peripheral arterial disease. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and 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 procedural 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 stem/progenitor cell therapy. The purpose of this review is to provide an outline of the preclinical basis for angiogenic and stem cell therapies, review the clinical research that has been done, summarize the lessons learned, identify gaps in knowledge, and suggest a course toward successfully addressing an unmet medical need in a large and growing patient population.