人iPSC来源的心肌细胞在药物筛选和组织再生中的最新进展

Yike Huang, Ting-zhong Wang, M. López, Minoru Hirano, A. Hasan, S. Shin
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引用次数: 4

摘要

心肌梗死和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。恢复心脏功能和用健康的再生心肌细胞(CMs)替代疤痕组织是治疗心力衰竭的一种有希望的方法。与其他心肌再生方法相比,人类诱导的多能干细胞(hiPSC)衍生的CMs (hiPSC-CMs)具有不存在重大伦理问题和可忽略的免疫排斥的优点。hiPSCs还可以产生无限数量的人类CMs,这是它们与其他心脏再生细胞来源相比的另一个优势。众多研究者致力于促进hiPSC-CMs的功能成熟,寻找各个分化阶段的精确调控机制,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。本文综述了提高hiPSC-CMs分化效率的各种方法,并讨论了hiPSC-CMs与成熟原生CMs之间电生理特性的差异。我们还介绍了获得大量iPSC-CMs的方法,这些方法需要实现生物制造策略,利用生物材料和先进的微制造技术的组合来构建仿生三维组织结构。基于特异性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疗提供未来的方向。22
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Recent advancements of human iPSC derived cardiomyocytes in drug screening and tissue regeneration
: 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. 22
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Erratum to Body-in-a-Cube: a microphysiological system for multi-tissue co-culture with near-physiological amounts of blood surrogate SARS-CoV-2-related vascular injury: mechanisms, imaging and models. Recent advancements of human iPSC derived cardiomyocytes in drug screening and tissue regeneration Body-in-a-Cube: a microphysiological system for multi-tissue co-culture with near-physiological amounts of blood surrogate. Engineering bone marrow-on-a-chip
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