McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Cardiovasc Res. 2023 Dec;2(12):1148-1158. doi: 10.1038/s44161-023-00377-w. Epub 2023 Dec 11.
Cardiovascular disease remains a leading cause of death worldwide despite important advances in modern medical and surgical therapies. As human adult cardiomyocytes have limited regenerative ability, cardiomyocytes lost after myocardial infarction are replaced by fibrotic scar tissue, leading to cardiac dysfunction and heart failure. To replace lost cardiomyocytes, a promising approach is direct cardiac reprogramming, in which cardiac fibroblasts are transdifferentiated into induced cardiomyocyte-like cells (iCMs). Here we review cardiac reprogramming cocktails (including transcription factors, microRNAs and small molecules) that mediate iCM generation. We also highlight mechanistic studies exploring the barriers to and facilitators of this process. We then review recent progress in iCM reprogramming, with a focus on single-cell '-omics' research. Finally, we discuss obstacles to clinical application.
尽管现代医学和外科治疗取得了重要进展，但心血管疾病仍然是全球主要的死亡原因。由于人类成体心肌细胞的再生能力有限，心肌梗死后丧失的心肌细胞被纤维瘢痕组织所取代，导致心功能障碍和心力衰竭。为了替代丧失的心肌细胞，一种很有前途的方法是直接心脏重编程，即心肌成纤维细胞转分化为诱导性心肌样细胞（iCM）。在这里，我们综述了介导 iCM 生成的心脏重编程鸡尾酒（包括转录因子、microRNAs 和小分子）。我们还强调了探索这一过程的障碍和促进因素的机制研究。然后，我们回顾了 iCM 重编程的最新进展，重点是单细胞“组学”研究。最后，我们讨论了临床应用的障碍。
