骨髓细胞移植在急性心肌梗死中的应用。

Stefan Janssens, Koen Theunissen, Marc Boogaerts, Frans Van de Werf
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引用次数: 31

摘要

缺血性损伤后心肌细胞的永久性丧失往往引发心力衰竭的发展,并对临床结果产生不利影响。祖细胞移植增强心脏修复的概念提出了新的治疗前景。在啮齿动物的早期研究中,使用各种形式的祖细胞转移在功能失调的心脏中,已经报告了有希望的结果,尽管潜在的机制仍然不明确。尽管干细胞在基因重编程后是否能够自主适应心肌细胞样行为,或者它们是否仅仅与原生宿主心肌细胞融合,仍存在争议,但早期临床试验已经显示出令人放心的安全性,并表明其功能益处。然而,确定心肌梗死后干细胞移植的内在价值需要精心设计的随机、安慰剂对照、盲法研究。虽然这些方法越来越可行,但仍需要考虑一些关键问题,如选择祖细胞类型、给药方案和给药时间,并且需要仔细选择未来临床试验的终点。缺血性心肌病患者对这种新的治疗模式有很大的热情,但只有在相关动物模型的临床前研究中仔细进行临床试验,才能最终确定细胞转移的最佳条件和适应症。
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Bone marrow cell transfer in acute myocardial infarction.

Permanent loss of cardiomyocytes after ischemic injury often initiates the development of heart failure and adversely affects clinical outcome. The concept of progenitor-cell transfer for enhancing cardiac repair has raised new therapeutic prospects. Promising results have been reported in early studies in rodents, using various modalities of progenitor-cell transfer in the dysfunctional heart, although underlying mechanisms remain ill defined. Despite ongoing controversies over whether or not stem cells can autonomously adapt cardiomyocyte-like behavior after genetic reprogramming or whether they merely fuse with native host cardiomyocytes, early-phase clinical trials have shown a reassuring safety profile and suggest a functional benefit. However, identification of the intrinsic value of stem cell transfer in patients after myocardial infarction will require carefully designed randomized, placebo-controlled, blinded studies. While these are becoming available, a number of critical questions about the choice of progenitor-cell type, dosage regimen, and timing of administration need to be considered, and end points for future clinical trials need to be chosen carefully. There is great enthusiasm for this novel treatment paradigm in patients with ischemic cardiomyopathy, but only carefully conducted clinical trials paralleled by preclinical studies in relevant animal models will ultimately identify the best conditions and indications for cell transfer.

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