PDF(Pubmed)
Abstract：
Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.
摘要：
利用由诱导多能干细胞(iPSC-CM)产生的心肌细胞的细胞疗法提供了作为慢性缺血性心脏病治疗的心脏再生的潜在途径。这里,我们报告了成功的长期植入和体内成熟的自体iPSC-CM在两个恒河猴与小，亚临床慢性心肌梗塞，都没有免疫抑制。使用钠/碘转运体（NIS）报告基因的纵向正电子发射断层扫描成像显示，移植物稳定超过6个月和12个月，没有畸胎瘤形成.组织学分析表明，移植的iPSC-CM成熟并与内源性心肌整合的能力，没有免疫细胞浸润或排斥的迹象。相比之下,同种异体iPSC-CM在移植后8周内被排斥。这项研究提供了迄今为止在任何大型动物模型中最长期的安全性和成熟度数据。解决了关于自体iPSC疗法的新抗原免疫反应性的问题，并表明自体iPSC-CM将类似地植入并在人类心脏中成熟。
