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从人诱导多能干细胞生产功能性心肌细胞和心脏组织用于再生治疗。

Production of functional cardiomyocytes and cardiac tissue from human induced pluripotent stem cells for regenerative therapy.

机构信息

Department of Cardiology, Keio University School of Medicine, Tokyo, Japan; Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan.

Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.

出版信息

J Mol Cell Cardiol. 2022 Mar;164:83-91. doi: 10.1016/j.yjmcc.2021.11.008. Epub 2021 Nov 22.

DOI:10.1016/j.yjmcc.2021.11.008
PMID:34822838
Abstract

The emergence of human induced pluripotent stem cells (hiPSCs) has revealed the potential for curing end-stage heart failure. Indeed, transplantation of hiPSC-derived cardiomyocytes (hiPSC-CMs) may have applications as a replacement for heart transplantation and conventional regenerative therapies. However, there are several challenges that still must be overcome for clinical applications, including large-scale production of hiPSCs and hiPSC-CMs, elimination of residual hiPSCs, purification of hiPSC-CMs, maturation of hiPSC-CMs, efficient engraftment of transplanted hiPSC-CMs, development of an injection device, and avoidance of post-transplant arrhythmia and immunological rejection. Thus, we developed several technologies based on understanding of the metabolic profiles of hiPSCs and hiPSC derivatives. In this review, we outline how to overcome these hurdles to realize the transplantation of hiPSC-CMs in patients with heart failure and introduce cutting-edge findings and perspectives for future regenerative therapy.

摘要

人诱导多能干细胞(hiPSC)的出现揭示了治疗终末期心力衰竭的潜力。事实上,hiPSC 衍生的心肌细胞(hiPSC-CMs)的移植可能适用于心脏移植和传统的再生疗法的替代。然而,仍有几个挑战需要克服,才能实现临床应用,包括大规模生产 hiPSC 和 hiPSC-CMs、消除残留的 hiPSC、纯化 hiPSC-CMs、hiPSC-CMs 的成熟、移植的 hiPSC-CMs 的有效植入、注射装置的开发以及避免移植后心律失常和免疫排斥。因此,我们基于对 hiPSC 和 hiPSC 衍生物代谢谱的理解,开发了几种技术。在这篇综述中,我们概述了如何克服这些障碍,实现在心力衰竭患者中移植 hiPSC-CMs,并介绍了未来再生治疗的最新发现和观点。

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