Improving Cardiac Reprogramming for Heart Regeneration in Translational Medicine.
Improving Cardiac Reprogramming for Heart Regeneration in Translational Medicine.
复制标题
在转化医学中改善心脏再生的心脏重编程。
作者：
Liu L;Guo Y;Li Z;Wang Z
直接将成纤维细胞重编程为cm样细胞已成为在心脏再生中产生诱导CMs （iCMs）的一种有吸引力的策略。然而，低转化率、低纯度、缺乏精确转化的洲际弹道导弹仍然是目前的重大挑战。在这篇综述中，我们总结了最近在理解心脏重编程的分子机制和各种策略以实现更有效的iCMs方面的进展。重新编程。具体来说，我们将重点关注心脏重编程中转录调控、表观遗传修饰、细胞微环境信号通路和细胞周期调控的关键作用。我们还讨论了与临床前应用相关的人类细胞中递送系统优化和心脏重编程的进展。我们预计这将把心脏重编程为基础的心脏治疗转化为临床应用。除了优化心脏发生相关的转录调控和信号通路外，一个重要的策略是调节与心脏损伤相关的病理微环境，包括炎症、促纤维化信号通路和受损心肌的力学特性。我们乐观地认为，心脏重编程将为心脏再生医学提供强有力的治疗方法。
Direct reprogramming of fibroblasts into CM-like cells has emerged as an attractive strategy to generate induced CMs (iCMs) in heart regeneration. However, low conversion rate, poor purity, and the lack of precise conversion of iCMs are still present as significant challenges. In this review, we summarize the recent development in understanding the molecular mechanisms of cardiac reprogramming with various strategies to achieve more efficient iCMs. reprogramming. Specifically, we focus on the identified critical roles of transcriptional regulation, epigenetic modification, signaling pathways from the cellular microenvironment, and cell cycling regulation in cardiac reprogramming. We also discuss the progress in delivery system optimization and cardiac reprogramming in human cells related to preclinical applications. We anticipate that this will translate cardiac reprogramming-based heart therapy into clinical applications. In addition to optimizing the cardiogenesis related transcriptional regulation and signaling pathways, an important strategy is to modulate the pathological microenvironment associated with heart injury, including inflammation, pro-fibrotic signaling pathways, and the mechanical properties of the damaged myocardium. We are optimistic that cardiac reprogramming will provide a powerful therapy in heart regenerative medicine.
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影响因子：
21.3
作者：
Garry GA;Bezprozvannaya S;Chen K;Zhou H;Hashimoto H;Morales MG;Liu N;Bassel-Duby R;Olson EN
通讯作者：
Olson EN
影响因子：
23.9
作者：
Fidalgo, Miguel;Huang, Xin;Guallar, Diana;Sanchez-Priego, Carlos;Valdes, Victor Julian;Saunders, Arven;Ding, Junjun;Wu, Wen-Shu;Clavel, Carlos;Wang, Jianlong
通讯作者：
Wang, Jianlong
影响因子：
56.9
作者：
Cao, Nan;Huang, Yu;Ding, Sheng
通讯作者：
Ding, Sheng
DOI：
10.1387/ijdb.103194hh
发表时间：
2010
期刊：
The International journal of developmental biology
影响因子：
--
作者：
Hirai H;Tani T;Kikyo N
通讯作者：
Kikyo N
影响因子：
3.7
作者：
Bektik E;Dennis A;Prasanna P;Madabhushi A;Fu JD
通讯作者：
Fu JD