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[心脏病学中的细胞治疗]

[Cellular therapy in cardiology].

作者信息

Menasché Philippe

机构信息

Département de chirurgie cardiovasculaire, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, université Paris-5, Inserm U633, 20, rue Leblanc, 75908 Paris cedex 15, France.

出版信息

C R Biol. 2007 Jun-Jul;330(6-7):550-6. doi: 10.1016/j.crvi.2007.05.004. Epub 2007 Jun 29.

Abstract

Cardiac cell therapy has been initially designed to regenerate the infarcted myocardium through its repopulation by new cells able to restore function of scar areas. Six years after the first human application of this novel approach, it is timely appropriate to review the results of the first randomised trials in the three major indications, i.e., acute myocardial infarction, heart failure, and refractory angina. It should be recognized that the results are mixed, with benefits ranging from absent to transient and, at most, marginal. However, lessons drawn from this first wave of clinical series and the experimental data that have been concomitantly collected are multiple and highly informative. They indicate that adult stem cells, whether muscular or bone marrow-derived, fail to generate new cardiomyocytes. They suggest that the potential benefits of cardiac cell therapy are thus mediated by alternate mechanisms such as limitation of left ventricular remodelling or paracrine activation of signalling pathways involved in angiogenesis. They highlight the fact that the therapeutic benefits of grafted cells will not be fully exploited until issues of cell transfer and postengraftment survival have not been adequately addressed. These observations thus allow us to better fine-tune upcoming research, which should specifically concentrate on the development of cells featuring a true regeneration potential. In this setting, the greatest promises are currently held by embryonic stem cells.

摘要

心脏细胞疗法最初旨在通过用能够恢复瘢痕区域功能的新细胞重新填充梗死心肌来实现心肌再生。在首次将这种新方法应用于人体六年之后,适时回顾一下在急性心肌梗死、心力衰竭和顽固性心绞痛这三大主要适应症方面的首批随机试验结果是很有必要的。应该认识到,结果喜忧参半,益处从无到短暂,最多也只是微不足道。然而,从这首批临床系列研究以及同时收集到的实验数据中吸取的经验教训众多且极具参考价值。这些经验教训表明,无论是肌肉来源还是骨髓来源的成体干细胞都无法生成新的心肌细胞。它们提示,心脏细胞疗法的潜在益处是通过诸如限制左心室重塑或旁分泌激活参与血管生成的信号通路等其他机制介导的。它们强调了这样一个事实,即在细胞移植和移植后存活问题尚未得到充分解决之前,移植细胞的治疗益处将无法得到充分发挥。因此,这些观察结果使我们能够更好地微调即将开展的研究,即将研究重点具体放在具有真正再生潜力的细胞的开发上。在这种情况下,胚胎干细胞目前最具前景。

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