Menasché Philippe
Department of Cardiovascular Surgery & INSERM U 572, Hôpital Européen Georges Pompidou, Paris, France.
Curr Opin Cardiol. 2004 Mar;19(2):154-61. doi: 10.1097/00001573-200403000-00016.
The last few years have witnessed a growing interest in regenerative therapy of the failing heart by cell transplantation. Special emphasis has been put on skeletal myoblasts and bone marrow-derived stem cells, with a flurry of experimental studies generating overall positive but occasionally conflicting results. It is thus appropriate to review the most important of these studies in light of the major issues that still impede widespread clinical use of cell therapy.
Recent laboratory data demonstrate the ability of autologous skeletal myoblasts to engraft into scarred myocardium and improve its function. Equally successful results have been reported with bone marrow-derived cells which, in contrast to myoblasts, are credited with a plasticity that might allow their transdifferentiation into cardiac or endothelial cells in response to organ-specific cues. However, some major questions remain unanswered; they include the choice of the optimal cell type in relation with the target patient population, the strategies for enhancing cell survival and functional integration, the clarification of the mechanisms of improvement, and the means of reducing invasiveness of cell delivery.
Although laboratory research attempts to overcome these persisting hurdles, the accumulated body of evidence warrants implementation of clinical trials. The earliest ones have now documented the feasibility of cell therapy. It is now appropriate to conduct safety and efficacy studies which, if carefully done, should allow assessment of the extent to which this concept of regenerative therapy can be made a clinical reality.
在过去几年中,细胞移植治疗衰竭心脏的再生疗法越来越受到关注。特别强调了骨骼肌成肌细胞和骨髓来源的干细胞,大量实验研究总体上产生了积极但偶尔相互矛盾的结果。因此,鉴于仍然阻碍细胞治疗广泛临床应用的主要问题,对这些研究中最重要的进行综述是恰当的。
最近的实验室数据表明自体骨骼肌成肌细胞能够植入瘢痕心肌并改善其功能。骨髓来源的细胞也报告了同样成功的结果,与成肌细胞不同,骨髓来源的细胞具有可塑性,可能使其根据器官特异性信号转分化为心肌细胞或内皮细胞。然而,一些主要问题仍未得到解答;它们包括与目标患者群体相关的最佳细胞类型的选择、提高细胞存活和功能整合的策略、改善机制的阐明以及降低细胞递送侵入性的方法。
尽管实验室研究试图克服这些持续存在的障碍,但积累的证据支持开展临床试验。最早的临床试验现已证明了细胞治疗的可行性。现在进行安全性和有效性研究是恰当的,如果仔细进行,应该能够评估这种再生治疗概念在多大程度上可以成为临床现实。