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利用人多能干细胞衍生心肌细胞进行心脏再生

Cardiac Regeneration with Human Pluripotent Stem Cell-Derived Cardiomyocytes.

作者信息

Park Misun, Yoon Young Sup

机构信息

Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

Korean Circ J. 2018 Nov;48(11):974-988. doi: 10.4070/kcj.2018.0312.

Abstract

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

摘要

胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs)统称为多能干细胞(PSCs),已成为再生医学中一种很有前景的细胞来源。特别是,人多能干细胞衍生的心肌细胞(hPSC-CMs)在再生受损心脏方面显示出强大的潜力。在过去二十年中,已开发出将hPSCs高效分化为心肌细胞的方案,为临床应用打开了大门。研究进一步证明了hPSC-CMs在大小动物模型中的治疗效果以及心脏修复的潜在机制。然而,对于移植的hPSC-CMs的治疗效果仍存在解释上的差距。此外,生物工程技术提高了hPSC-CMs在体内的存活率和治疗效果。虽然与使用hPSCs相关的大多数最初问题已得到解决,但仍有几个问题有待解决,例如移植细胞的不成熟、缺乏电整合导致致心律失常风险以及致瘤性。用hPSC-CMs进行细胞治疗在受损心脏的生物治疗中显示出巨大潜力;然而,在这项技术能够临床应用之前,还需要更多的研究来确保治疗效果、潜在机制和安全性。

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