Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy.
Cells. 2023 Apr 15;12(8):1166. doi: 10.3390/cells12081166.
Cardiac diseases are the foremost cause of morbidity and mortality worldwide. The heart has limited regenerative potential; therefore, lost cardiac tissue cannot be replenished after cardiac injury. Conventional therapies are unable to restore functional cardiac tissue. In recent decades, much attention has been paid to regenerative medicine to overcome this issue. Direct reprogramming is a promising therapeutic approach in regenerative cardiac medicine that has the potential to provide in situ cardiac regeneration. It consists of direct cell fate conversion of one cell type into another, avoiding transition through an intermediary pluripotent state. In injured cardiac tissue, this strategy directs transdifferentiation of resident non-myocyte cells (NMCs) into mature functional cardiac cells that help to restore the native tissue. Over the years, developments in reprogramming methods have suggested that regulation of several intrinsic factors in NMCs can help to achieve in situ direct cardiac reprogramming. Among NMCs, endogenous cardiac fibroblasts have been studied for their potential to be directly reprogrammed into both induced cardiomyocytes and induced cardiac progenitor cells, while pericytes can transdifferentiate towards endothelial cells and smooth muscle cells. This strategy has been indicated to improve heart function and reduce fibrosis after cardiac injury in preclinical models. This review summarizes the recent updates and progress in direct cardiac reprogramming of resident NMCs for in situ cardiac regeneration.
心脏病是全球发病率和死亡率的首要原因。心脏的再生潜力有限；因此，心脏损伤后不能补充丢失的心肌组织。传统疗法无法恢复功能性心肌组织。近几十年来，人们越来越关注再生医学来解决这个问题。直接重编程是再生心脏医学中一种很有前途的治疗方法，它有可能提供原位心脏再生。它包括将一种细胞类型直接转化为另一种细胞类型，避免通过中间多能状态进行转化。在受损的心肌组织中，这种策略指导驻留非心肌细胞（NMC）向成熟的功能性心肌细胞的转分化，有助于恢复原生组织。多年来，重编程方法的发展表明，调节 NMC 中的几种内在因素有助于实现原位直接心脏重编程。在 NMC 中，内源性心肌成纤维细胞已被研究用于直接重编程为诱导性心肌细胞和诱导性心肌祖细胞，而周细胞可向内皮细胞和平滑肌细胞转分化。在临床前模型中，该策略已被证明可改善心脏功能并减少心脏损伤后的纤维化。本文综述了近年来驻留 NMC 的直接心脏重编程用于原位心脏再生的最新进展。
