Key Success Factors for Regenerative Medicine in Acquired Heart Diseases
Key Success Factors for Regenerative Medicine in Acquired Heart Diseases
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DOI：
10.1007/s12015-020-09961-0
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发表时间：
2020-04-15
影响因子：
4.8
通讯作者：
Henon, Philippe
中科院分区：
文献类型：
--
作者：
Henon, Philippe
干细胞治疗为改善缺血性心脏病提供了突破性的机会。许多临床试验和荟萃分析似乎证实了其对心脏功能的积极但可变的影响。尽管这些试验在设计、细胞类型、来源和再注射剂量、细胞注射途径和时间以及心脏病类型方面存在很大差异，但可能有利于细胞治疗成功的关键因素来自对其数据的审查。已经交付了各种类型的细胞。注射成肌细胞不能改善心脏功能，并且常常导致严重的室性心律失常的发生。使用骨髓单个核细胞是一种误解，因为它们不是干细胞，而是主要是造血谱系和基质细胞的各种细胞的混合物，仅含有非常少量的具有干细胞样特征的细胞;这可能解释了中性结果，或者最多解释了注射后报告的心脏功能的适度改善。心脏干细胞的真实存在现在似乎非常不可信，至少在成年人中是这样。间充质干细胞不能修复受损的心肌组织，但能减弱梗死后的重塑，并有助于瘢痕周围冬眠区的血管重建。CD 34（+）干细胞--可能来自多能性极小胚胎样（VSEL）干细胞--成为最令人信服的细胞类型，诱导缺血心肌区域的结构和功能修复，前提是它们可以通过心肌内而不是冠状动脉内注射大量递送，并且优先在心肌梗死后而不是慢性心力衰竭后递送。
Stem cell therapy offers a breakthrough opportunity for the improvement of ischemic heart diseases. Numerous clinical trials and meta-analyses appear to confirm its positive but variable effects on heart function. Whereas these trials widely differed in design, cell type, source, and doses reinjected, cell injection route and timing, and type of cardiac disease, crucial key factors that may favour the success of cell therapy emerge from the review of their data. Various types of cell have been delivered. Injection of myoblasts does not improve heart function and is often responsible for severe ventricular arrythmia occurrence. Using bone marrow mononuclear cells is a misconception, as they are not stem cells but mainly a mix of various cells of hematopoietic lineages and stromal cells, only containing very low numbers of cells that have stem cell-like features; this likely explain the neutral results or at best the modest improvement in heart function reported after their injection. The true existence of cardiac stem cells now appears to be highly discredited, at least in adults. Mesenchymal stem cells do not repair the damaged myocardial tissue but attenuate post-infarction remodelling and contribute to revascularization of the hibernated zone surrounding the scar. CD34(+) stem cells - likely issued from pluripotent very small embryonic-like (VSEL) stem cells - emerge as the most convincing cell type, inducing structural and functional repair of the ischemic myocardial area, providing they can be delivered in large amounts via intra-myocardial rather than intra-coronary injection, and preferentially after myocardial infarct rather than chronic heart failure.