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人诱导多能干细胞衍生心肌细胞在药物筛选和组织再生方面的最新进展。

Recent advancements of human iPSC derived cardiomyocytes in drug screening and tissue regeneration.

作者信息

Huang Yike, Wang Ting, López María Elizabeth Urbina, Hirano Minoru, Hasan Anwarul, Shin Su Ryon

机构信息

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA.

Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, China.

出版信息

Microphysiol Syst. 2020 Sep;4:2. doi: 10.21037/mps-20-3. Epub 2020 Sep 15.

Abstract

Myocardial infarction together with subsequent heart failures are among the main reasons for death related to cardiovascular diseases (CVD). Restoring cardiac function and replacing scar tissue with healthy regenerated cardiomyocytes (CMs) is a hopeful therapy for heart failure. Human-induced pluripotent stem cell (hiPSC) derived CMs (hiPSC-CMs) offer the advantages of not having significant ethical issues and having negligible immunological rejection compared to other myocardial regeneration methods. hiPSCs can also produce an unlimited number of human CMs, another advantage they have compared with other cell sources for cardiac regeneration. Numerous researchers have focused their work on promoting the functional maturity of hiPSC-CMs, as well as finding out the precise regulatory mechanisms of each differentiation stage together with the economical and practical methods of acquisition and purification. However, the clinical applications of hiPSC-CMs in drug discovery and cardiac regeneration therapy have yet to be achieved. In this review, we present an overview of various methods for improving the differentiation efficiency of hiPSC-CMs and discuss the differences of electrophysiological characteristics between hiPSC-CMs and matured native CMs. We also introduce approaches for obtaining a large quantity of iPSC-CMs, which are needed to achieve biomanufacturing strategies for building biomimetic three-dimensional tissue constructs using combinations of biomaterials and advanced microfabrication techniques. Recent advances in specific iPSC technology-based drug screening platforms and regeneration therapies can suggest future directions for personalized medicine in biomedical applications.

摘要

心肌梗死以及随后的心力衰竭是心血管疾病(CVD)相关死亡的主要原因之一。恢复心脏功能并用健康的再生心肌细胞(CMs)替代瘢痕组织是治疗心力衰竭的一种有前景的方法。与其他心肌再生方法相比,人诱导多能干细胞(hiPSC)衍生的CMs(hiPSC-CMs)具有不存在重大伦理问题且免疫排斥可忽略不计的优点。hiPSC还可以产生无限数量的人CMs,这是它们与其他用于心脏再生的细胞来源相比所具有的另一个优势。众多研究人员将工作重点放在促进hiPSC-CMs的功能成熟上,以及找出每个分化阶段的确切调控机制以及经济实用的获取和纯化方法。然而,hiPSC-CMs在药物发现和心脏再生治疗中的临床应用尚未实现。在这篇综述中,我们概述了提高hiPSC-CMs分化效率的各种方法,并讨论了hiPSC-CMs与成熟的天然CMs之间电生理特征的差异。我们还介绍了获得大量iPSC-CMs的方法,这是实现使用生物材料和先进微制造技术组合构建仿生三维组织构建体的生物制造策略所必需的。基于特定iPSC技术的药物筛选平台和再生疗法的最新进展可以为生物医学应用中的个性化医学指明未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e18a/11488690/51289f0818c4/nihms-1984597-f0001.jpg

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