Andrianto Andrianto, Mulia Eka Prasetya Budi, Luke Kevin
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga - Dr. Soetomo General Hospital, Mayjen Prof. Dr. Moestopo Street No.6-8, 60286, Surabaya, Indonesia.
Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Mol Biol Rep. 2023 Jan;50(1):865-871. doi: 10.1007/s11033-022-07913-0. Epub 2022 Oct 29.
Heart failure is the leading cause of morbidity and mortality worldwide and is characterized by reduced cardiac function. Currently, cardiac transplantation therapy is applied for end-stage heart failure, but it is limited by the number of available donors.
Following an assessment of available literature, a narrative review was conducted to summarizes the current status and challenges of cardiac reprogramming for clinical application. Scientists have developed different regenerative treatment strategies for curing heart failure, including progenitor cell delivery and pluripotent cell delivery. Recently, a novel strategy has emerged that directly reprograms cardiac fibroblast into a functional cardiomyocyte. In this treatment, transcription factors are first identified to reprogram fibroblast into a cardiomyocyte. After that, microRNA and small molecules show great potential to optimize the reprogramming process. Some challenges regarding cell reprogramming in humans are conversion efficiency, virus utilization, immature and heterogenous induced cardiomyocytes, technical reproducibility issues, and physiological effects of depleted fibroblasts on myocardial tissue.
Several strategies have shown positive results in direct cardiac reprogramming. However, direct cardiac reprogramming still needs improvement if it is used as a mainstay therapy in humans, and challenges need to be overcome before cardiac reprogramming can be considered a viable therapeutic strategy. Further advances in cardiac reprogramming studies are needed in cardiac regenerative therapy.
心力衰竭是全球发病和死亡的主要原因，其特征是心脏功能降低。目前，心脏移植疗法用于终末期心力衰竭，但受到可用供体数量的限制。
在对现有文献进行评估后，进行了一项叙述性综述，以总结心脏重编程临床应用的现状和挑战。科学家们已经开发出不同的再生治疗策略来治疗心力衰竭，包括祖细胞递送和多能细胞递送。最近，出现了一种新策略，可将心脏成纤维细胞直接重编程为功能性心肌细胞。在这种治疗中，首先确定转录因子将成纤维细胞重编程为心肌细胞。之后，微小RNA和小分子在优化重编程过程方面显示出巨大潜力。人类细胞重编程存在一些挑战，包括转化效率、病毒利用、诱导心肌细胞不成熟和异质性、技术可重复性问题以及成纤维细胞耗竭对心肌组织的生理影响。
几种策略在直接心脏重编程中已显示出积极结果。然而，如果将直接心脏重编程用作人类的主要治疗方法，仍需改进，并且在心脏重编程被视为可行的治疗策略之前，需要克服各种挑战。心脏再生治疗需要心脏重编程研究取得进一步进展。
