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Non-coding RNAs: key regulators of reprogramming, pluripotency, and cardiac cell specification with therapeutic perspective for heart regeneration
Cardiovascular Research ( IF 10.8 ) Pub Date : 2021-10-27 , DOI: 10.1093/cvr/cvab335
Hannah J Hunkler 1 , Sonja Groß 1 , Thomas Thum 1, 2, 3 , Christian Bär 1, 2
Affiliation  

Myocardial infarction causes a massive loss of cardiomyocytes (CMs), which can lead to heart failure accompanied by fibrosis, stiffening of the heart, and loss of function. Heart failure causes high mortality rates and is a huge socioeconomic burden, which, based on diets and lifestyle in the developed world, is expected to increase further in the next years. At present, the only curative treatment for heart failure is heart transplantation associated with a number of limitations such as donor organ availability and transplant rejection among others. Thus, the development of cellular reprogramming and defined differentiation protocols provide exciting new possibilities for cell therapy approaches and which opened up a new era in regenerative medicine. Consequently, tremendous research efforts were undertaken to gain a detailed molecular understanding of the reprogramming processes and the in vitro differentiation of pluripotent stem cells into functional CMs for transplantation into the patient’s injured heart. In the last decade, non-coding RNAs, particularly microRNAs, long non-coding RNAs, and circular RNAs emerged as critical regulators of gene expression that were shown to fine-tune cellular processes both on the transcriptional and the post-transcriptional level. Unsurprisingly, also cellular reprogramming, pluripotency, and cardiac differentiation and maturation are regulated by non-coding RNAs. In here, we review the current knowledge on non-coding RNAs in these processes and highlight how their modulation may enhance the quality and quantity of stem cells and their derivatives for safe and efficient clinical application in patients with heart failure. In addition, we summarize the clinical cell therapy efforts undertaken thus far.

中文翻译:

非编码 RNA:重编程、多能性和心脏细胞规格的关键调节因子,具有心脏再生的治疗前景

心肌梗塞会导致心肌细胞 (CM) 大量丢失,从而导致心力衰竭并伴有纤维化、心脏硬化和功能丧失。心力衰竭导致高死亡率,是一个巨大的社会经济负担,根据发达国家的饮食和生活方式,预计未来几年会进一步增加。目前,心力衰竭的唯一治疗方法是心脏移植,但存在许多限制,例如供体器官可用性和移植排斥等。因此,细胞重编程和定义的分化方案的发展为细胞治疗方法提供了令人兴奋的新可能性,并开辟了再生医学的新纪元。最后,进行了大量的研究工作,以获得对重编程过程和多能干细胞体外分化为功能性 CM 以移植到患者受伤心脏中的详细分子理解。在过去的十年中,非编码 RNA,特别是 microRNA、长链非编码 RNA 和环状 RNA 成为基因表达的关键调节因子,被证明可以在转录和转录后水平上微调细胞过程。不出所料,细胞重编程、多能性以及心脏分化和成熟也受非编码 RNA 调控。在这里,我们回顾了这些过程中非编码 RNA 的当前知识,并强调了它们的调节如何提高干细胞及其衍生物的质量和数量,以便安全有效地临床应用于心力衰竭患者。此外,我们总结了迄今为止进行的临床细胞治疗工作。
更新日期:2021-10-27
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