The Present State and Future Perspectives of Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells.
The Present State and Future Perspectives of Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells.
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DOI：
10.3389/fcvm.2021.774389
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发表时间：
2021
影响因子：
3.6
通讯作者：
Tohyama S
中科院分区：
文献类型：
--
作者：
Soma Y;Morita Y;Kishino Y;Kanazawa H;Fukuda K;Tohyama S
随着人口老龄化，心力衰竭（HF）患者的数量在全球范围内不断增加。对药物和器械治疗有耐药性的心衰患者是心脏移植（HT）的候选者。然而，捐献心脏的短缺是一个严重的问题。利用人类多能干细胞（human pluripotent stem cells, hPSCs），如人类胚胎干细胞和诱导多能干细胞，作为替代HT的心脏再生治疗有望实现。通过模拟正常心脏发育，促进了造血干细胞向心肌细胞（CMs）的分化。为了防止移植后的肿瘤发生，重要的是消除非CMs，包括残留的hPSCs，只选择CMs。在许多CMs选择系统中，基于CMs和非CMs之间代谢差异的代谢选择在成本和功效方面都是有利的。大规模培养系统已经被开发出来，因为临床移植需要大量的hpsc来源的CMs （hPSC-CMs）。在大型动物模型中，hPSC-CMs移植到心肌中可以改善心肌梗死模型的心功能。虽然移植后心律失常和免疫排斥仍然是问题，但其机制和解决方案正在研究中。通过这种方式，心脏再生治疗的问题正在得到单独解决。因此，hPSC-CMs的心脏再生治疗有望在不久的将来成为一种安全有效的心衰治疗方法。在这篇综述中，我们描述了与hPSC-CMs相关的先前研究，并讨论了使用hPSC-CMs进行心脏再生治疗的未来前景。
The number of patients with heart failure (HF) is increasing with aging in our society worldwide. Patients with HF who are resistant to medication and device therapy are candidates for heart transplantation (HT). However, the shortage of donor hearts is a serious issue. As an alternative to HT, cardiac regenerative therapy using human pluripotent stem cells (hPSCs), such as human embryonic stem cells and induced pluripotent stem cells, is expected to be realized. Differentiation of hPSCs into cardiomyocytes (CMs) is facilitated by mimicking normal heart development. To prevent tumorigenesis after transplantation, it is important to eliminate non-CMs, including residual hPSCs, and select only CMs. Among many CM selection systems, metabolic selection based on the differences in metabolism between CMs and non-CMs is favorable in terms of cost and efficacy. Large-scale culture systems have been developed because a large number of hPSC-derived CMs (hPSC-CMs) are required for transplantation in clinical settings. In large animal models, hPSC-CMs transplanted into the myocardium improved cardiac function in a myocardial infarction model. Although post-transplantation arrhythmia and immune rejection remain problems, their mechanisms and solutions are under investigation. In this manner, the problems of cardiac regenerative therapy are being solved individually. Thus, cardiac regenerative therapy with hPSC-CMs is expected to become a safe and effective treatment for HF in the near future. In this review, we describe previous studies related to hPSC-CMs and discuss the future perspectives of cardiac regenerative therapy using hPSC-CMs.