Abstract:
Cardiac regenerative therapy using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is expected to become an alternative to heart transplantation for severe heart failure. It is now possible to produce large numbers of human pluripotent stem cells (hPSCs) and eliminate non-cardiomyocytes, including residual undifferentiated hPSCs, which can cause teratoma formation after transplantation. There are two main strategies for transplanting hPSC-CMs: injection of hPSC-CMs into the myocardium from the epicardial side, and implantation of hPSC-CM patches or engineered heart tissues onto the epicardium. Transplantation of hPSC-CMs into the myocardium of large animals in a myocardial infarction model improved cardiac function. The engrafted hPSC-CMs matured, and microvessels derived from the host entered the graft abundantly. Furthermore, as less invasive methods using catheters, injection into the coronary artery and injection into the myocardium from the endocardium side have recently been investigated. Since transplantation of hPSC-CMs alone has a low engraftment rate, various methods such as transplantation with the extracellular matrix or non-cardiomyocytes and aggregation of hPSC-CMs have been developed. Post-transplant arrhythmias, imaging of engrafted hPSC-CMs, and immune rejection are the remaining major issues, and research is being conducted to address them. The clinical application of cardiac regenerative therapy using hPSC-CMs has just begun and is expected to spread widely if its safety and efficacy are proven in the near future.
摘要:
使用人多能干细胞衍生的心肌细胞(hPSC-CM)的心脏再生疗法有望成为严重心力衰竭的心脏移植的替代方法。现在可以产生大量的人类多能干细胞(hPSC)并消除非心肌细胞,包括残留的未分化hPSC,移植后可导致畸胎瘤形成。hPSC-CM移植有两种主要策略:从心外膜侧向心肌注射hPSC-CM,并将hPSC-CM补片或工程心脏组织植入心外膜。在心肌梗死模型中将hPSC-CM移植到大型动物的心肌中改善了心脏功能。嫁接的hPSC-CM成熟了,来自宿主的微血管大量进入移植物。此外,作为使用导管的侵入性较小的方法,最近研究了注射到冠状动脉和从心内膜侧注射到心肌中。由于单独移植hPSC-CM的植入率低,已经开发了各种方法,例如用细胞外基质或非心肌细胞移植和hPSC-CM的聚集。移植后心律失常,移植的hPSC-CM的成像,免疫排斥是剩下的主要问题,正在进行研究以解决这些问题。使用hPSC-CM的心脏再生疗法的临床应用刚刚开始,如果其安全性和有效性在不久的将来得到证实,则有望广泛传播。