Vassalli G, Vanderheyden M, Renders F, Eeckhout E, Bartunek J
Department of Cardiology, CHUV University Hospital, Lausanne, Switzerland.
Minerva Cardioangiol. 2007 Oct;55(5):659-67.
Bone marrow (BM) stem cells can differentiate into multiple cell types, including vascular cells and, possibly, cardiac myocytes. Stem and progenitor cells are mobilized into the peripheral circulation early after myocardial infarction. Experimental evidence suggests that BM-derived cells injected into infarcted hearts can improve cardiac function. However, mechanisms underlying functional improvements remain unclear. Initial randomized, placebo-controlled trials in patients with acute myocardial infarction have provided controversial
On the one hand, a modest but significant and sustained improvement in left ventricular function was observed in the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study contributing to the better clinical course. Results of other studies were neutral. Differences in the study design, cell processing or timing of cell delivery might explain, in part, different outcomes among studies. Furthermore, studies in patients with chronic ischemic heart disease remain observational, and therapeutic effects using surrogate end-points needs to be demonstrated. Thus, there is a need for further coordinated research with well designed, hypothesis-driven clinical trials, in parallel with fundamental research aimed at understanding the mechanisms underlying the biological and functional effects of BM cell therapy for cardiac repair.
骨髓(BM)干细胞可分化为多种细胞类型,包括血管细胞,也可能分化为心肌细胞。在心肌梗死后早期,干细胞和祖细胞会被动员到外周循环中。实验证据表明,注入梗死心脏的骨髓来源细胞可改善心脏功能。然而,功能改善的潜在机制仍不清楚。最初针对急性心肌梗死患者进行的随机、安慰剂对照试验得出了有争议的结果。一方面,在急性心肌梗死中富集祖细胞再输注与梗死重塑(REPAIR-AMI)研究中观察到左心室功能有适度但显著且持续的改善,这有助于更好的临床病程。其他研究结果则为中性。研究设计、细胞处理或细胞递送时间的差异可能部分解释了各研究结果的不同。此外,针对慢性缺血性心脏病患者的研究仍为观察性研究,需要证明使用替代终点的治疗效果。因此,需要进一步开展精心设计、以假设为驱动的临床试验的协调研究,同时进行基础研究,旨在了解骨髓细胞治疗心脏修复的生物学和功能效应的潜在机制。