Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0529, USA.
Int J Mol Sci. 2020 Oct 16;21(20):7662. doi: 10.3390/ijms21207662.
Limited adult cardiac cell proliferation after cardiovascular disease, such as heart failure, hampers regeneration, resulting in a major loss of cardiomyocytes (CMs) at the site of injury. Recent studies in cellular reprogramming approaches have provided the opportunity to improve upon previous techniques used to regenerate damaged heart. Using these approaches, new CMs can be regenerated from differentiation of iPSCs (similar to embryonic stem cells), the direct reprogramming of fibroblasts [induced cardiomyocytes (iCMs)], or induced cardiac progenitors. Although these CMs have been shown to functionally repair infarcted heart, advancements in technology are still in the early stages of development in research laboratories. In this review, reprogramming-based approaches for generating CMs are briefly introduced and reviewed, and the challenges (including low efficiency, functional maturity, and safety issues) that hinder further translation of these approaches into a clinical setting are discussed. The creative and combined optimal methods to address these challenges are also summarized, with optimism that further investigation into tissue engineering, cardiac development signaling, and epigenetic mechanisms will help to establish methods that improve cell-reprogramming approaches for heart regeneration.
心血管疾病（如心力衰竭）后，成人心脏细胞的增殖受到限制，这阻碍了再生，导致损伤部位大量心肌细胞（CMs）丢失。细胞重编程方法的最新研究为改善以前用于再生受损心脏的技术提供了机会。使用这些方法，可以从诱导多能干细胞（类似于胚胎干细胞）的分化、成纤维细胞的直接重编程[诱导心肌细胞（iCMs）]或诱导性心肌前体细胞中再生新的 CMs。尽管这些 CMs 已被证明可以功能性修复梗死的心脏，但技术的进步仍处于研究实验室的早期发展阶段。在这篇综述中，简要介绍和回顾了基于重编程的生成 CMs 的方法，并讨论了阻碍这些方法进一步转化为临床应用的挑战（包括效率低、功能成熟度和安全问题）。还总结了创造性和组合的最佳方法来解决这些挑战，乐观地认为进一步研究组织工程、心脏发育信号和表观遗传机制将有助于建立改善心脏再生细胞重编程方法的方法。
