Department of Regenerative Science and Medicine, Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Curr Cardiol Rep. 2019 Jun 21;21(8):73. doi: 10.1007/s11886-019-1171-3.
Cardiovascular disease is the leading cause of mortality worldwide. Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have great potential to treat heart disease, owing to their capacity of engraftment and remuscularization in the host heart after transplantation. In the current review, we provide an overview of PSC-CMs for clinical transplantation.
Studies have shown that PSC-CMs can survive, engraft, and form gap junctions after transplantation, with functional benefit. Engrafted PSC-CMs matured gradually in host hearts. Only in a large animal model, transient ventricular arrhythmias were detected, mainly because of the ectopic pacing from the grafted PSC-CMs. Although intense immunosuppression is unavoidable in xenotransplantation, immunosuppression remains necessary for MHC-matched allogenic non-human primate PSC-CMs transplantation. This review offers insights on how PSC-CMs contribute to functional benefit after transplantation to injured non-human primate hearts. We believe that PSC-CM transplantation represents a potentially novel treatment for ischemic heart diseases, provided that several technological and biological limitations can be overcome.
心血管疾病是全球范围内导致死亡的主要原因。多能干细胞衍生的心肌细胞(PSC-CMs)具有在移植后在宿主心脏中植入和再肌化的能力,有望用于治疗心脏病。在本综述中,我们对 PSC-CMs 用于临床移植进行了概述。
研究表明,PSC-CMs 移植后可以存活、植入并形成间隙连接,具有功能益处。植入的 PSC-CMs 在宿主心脏中逐渐成熟。只有在大型动物模型中,才检测到短暂性室性心律失常,主要是由于来自移植的 PSC-CMs 的异位起搏。尽管异种移植不可避免地需要强烈的免疫抑制,但 MHC 匹配的同种异体非人类灵长类 PSC-CMs 移植仍需要免疫抑制。本综述提供了关于 PSC-CMs 在损伤的非人类灵长类动物心脏移植后如何促进功能益处的见解。我们相信,PSC-CM 移植代表了一种有前途的缺血性心脏病治疗方法,前提是可以克服一些技术和生物学限制。