Toronto General Research Institute, McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada.
Toronto General Research Institute, McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Curr Opin Biotechnol. 2017 Oct;47:43-50. doi: 10.1016/j.copbio.2017.05.011. Epub 2017 Jun 17.
Because the heart is a poorly regenerative organ, there has been considerable interest in developing novel cell-based approaches to restore lost contractile function after myocardial infarction (MI). While a wide variety of candidate cell types have been tested in animal MI models, the vast majority of clinical trials have used adult stem cell types, usually derived from bone marrow. These studies have generally yielded disappointing results, an outcome that may reflect in part the limited cardiogenic potential of the adult stem cell sources employed. Post-MI heart failure is ultimately a disease of cardiomyocyte deficiency, so better outcomes may be possible with more cardiogenic approaches that may 'remuscularize' the infarct scar with new, electrically-integrated myocardium. In this review, we summarize work in the field to 'program' exogenous or endogenous cells into such a cardiogenic state, as well as efforts to test their capacity to mediate true heart regeneration.
由于心脏的再生能力很差，因此人们一直非常关注开发新的基于细胞的方法，以在心肌梗死 (MI) 后恢复丧失的收缩功能。虽然已经在动物 MI 模型中测试了多种候选细胞类型，但绝大多数临床试验都使用了成年干细胞类型，通常来自骨髓。这些研究的结果通常令人失望，这一结果可能部分反映了所使用的成年干细胞来源的有限的心脏生成潜力。MI 后心力衰竭最终是一种心肌细胞缺乏症，因此采用更具心脏生成能力的方法可能会获得更好的效果，这些方法可能会用新的、电整合的心肌“重塑”梗死瘢痕。在这篇综述中，我们总结了将外源性或内源性细胞“编程”为这种心脏生成状态的工作，以及测试它们介导真正心脏再生的能力的努力。
