Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany.
FASEB J. 2019 Jan;33(1):49-70. doi: 10.1096/fj.201800712R. Epub 2018 Sep 6.
To date, no viable therapeutic options exist for the effective and sustained reversal of cardiac failure, other than heart transplantation and mechanical circulatory assist devices. Therefore, divergent strategies aiming at the de novo formation of contractile tissue, as a prerequisite for the restoration of cardiac pump function, are currently being pursued. Clinical trials involving the transplantation of somatic progenitor cells failed. The search for alternative cell-based strategies to combat the consequences of ischemic injury has sparked widespread interest in the genetic and pharmacologic reprogramming of fibroblasts into cardiomyocytes, harnessing the abundant in vivo pool of cardiac fibroblasts. Here, we provide a comprehensive overview of in vitro and in vivo cardiac reprogramming studies identified in an extensive literature search. We systematically review and evaluate feasibility, efficiency, and reproducibility of the different technologies currently being explored. Finally, we discuss potential safety issues deduced from preclinical studies and identify obstacles that must be overcome before clinical translation.-Klose, K., Gossen, M., Stamm, C. Turning fibroblasts into cardiomyocytes: technological review of cardiac transdifferentiation strategies.
迄今为止，除心脏移植和机械循环辅助装置外，尚无有效的、可持续的心力衰竭逆转治疗方法。因此，目前正在探索旨在使收缩性组织从头形成的不同策略，作为恢复心脏泵功能的前提条件。涉及体细胞核移植的临床试验失败了。寻找替代的基于细胞的策略来对抗缺血性损伤的后果，引起了人们对基因和药理学将成纤维细胞重编程为心肌细胞以利用体内丰富的心肌成纤维细胞的广泛兴趣。在这里，我们提供了在广泛的文献检索中确定的体外和体内心脏重编程研究的综合概述。我们系统地审查和评估了目前正在探索的不同技术的可行性、效率和可重复性。最后，我们讨论了从临床前研究中推断出的潜在安全问题，并确定了在临床转化之前必须克服的障碍。-Klose, K., Gossen, M., Stamm, C. 将成纤维细胞转化为心肌细胞：心脏转分化策略的技术综述。
