Cell therapy of peripheral arterial disease: from experimental findings to clinical trials.
Cell therapy of peripheral arterial disease: from experimental findings to clinical trials.
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DOI：
10.1161/circresaha.113.300565
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发表时间：
2013-04-26
影响因子：
20.1
通讯作者：
Losordo DW
中科院分区：
文献类型：
--
作者：
Raval Z;Losordo DW
1985年，美国人群中外周动脉疾病的年龄调整患病率估计接近12%，随着人群老龄化，预计患有外周动脉疾病的总人群将增加。闭塞性外周动脉疾病的临床后果包括间歇性跛行（即行走疼痛）和严重肢体缺血（CLI）（包括静息疼痛和远端肢体组织完整性丧失，最终可能导致下肢部分截肢）。CLI的危险因素与冠状动脉疾病的危险因素相似，包括高龄、吸烟、糖尿病、高脂血症和高血压。据估计，1991年全球CLI的发病率为每年每百万人500至1000例。对于患有晚期肢体疾病的CLI受试者，预后较差。英国一项对400多名此类受试者的研究发现，25%的受试者需要截肢，20%（包括一些需要截肢的受试者）在1年内死亡。在美国，每年每百万人中有10280例因缺血性疾病而进行的下肢截肢。治疗CLI的首要目标是增加患肢的血液循环。从理论上讲，增加血流量可以通过增加向缺血组织供血的血管数量来实现。使用药理学试剂来诱导新血管生长以治疗或预防病理临床病症被称为治疗性血管生成。自1997年Asahara和Isner鉴定出内皮祖细胞以来，外周动脉疾病的细胞治疗领域一直处于不断发展的状态。在这里，我们回顾了该领域的现状。
The age-adjusted prevalence of peripheral arterial disease in the US population was estimated to approach 12% in 1985, and as the population ages, the overall population having peripheral arterial disease is predicted to rise. The clinical consequences of occlusive peripheral arterial disease include intermittent claudication, that is, pain with walking, and critical limb ischemia (CLI), which includes pain at rest and loss of tissue integrity in the distal limbs, which may ultimately lead to amputation of a portion of the lower extremity. The risk factors for CLI are similar to those linked to coronary artery disease and include advanced age, smoking, diabetes mellitus, hyperlipidemia, and hypertension. The worldwide incidence of CLI was estimated to be 500 to 1000 cases per million people per year in 1991. The prognosis is poor for CLI subjects with advanced limb disease. One study of >400 such subjects in the United Kingdom found that 25% required amputation and 20% (including some subjects who had required amputation) died within 1 year. In the United States, ≈280 lower-limb amputations for ischemic disease are performed per million people each year. The first objective in treating CLI is to increase blood circulation to the affected limb. Theoretically, increased blood flow could be achieved by increasing the number of vessels that supply the ischemic tissue with blood. The use of pharmacological agents to induce new blood vessel growth for the treatment or prevention of pathological clinical conditions has been called therapeutic angiogenesis. Since the identification of the endothelial progenitor cell in 1997 by Asahara and Isner, the field of cell-based therapies for peripheral arterial disease has been in a state of continuous evolution. Here, we review the current state of that field.