美国华盛顿大学Cynthia E. Dunbar小组报道，自体iPSC来源心肌细胞在两只恒河猴体内的长期植入和成熟。这一研究成果发表在2024年6月5日出版的国际学术期刊《细胞—干细胞》上。

研究人员表示，利用诱导多能干细胞(iPSC-CMs)产生的心肌细胞进行细胞治疗，为慢性缺血性心脏病的心脏再生提供了一条潜在的途径。

该课题组人员报道了在两只患有轻微、亚临床慢性心肌梗死的恒河猴中，成功实现了自体诱导多能干细胞衍生的心肌细胞（iPSC-CMs）的长期植入和体内成熟，且无需免疫抑制。使用钠/碘同向转运体（NIS）报告基因进行的纵向正电子发射断层扫描成像显示，移植物在6个月和12个月以上均保持稳定，且无畸胎瘤形成。

组织学分析表明，移植的iPSC-CMs具备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，异体iPSC-CMs在移植8周内被排斥。本研究提供了迄今为止在任何大型动物模型中最长时间的安全性和成熟性数据，解决了关于自体iPSC疗法新抗原免疫反应性的担忧，并表明自体iPSC-CMs在人体心脏中同样可以植入和成熟。

附：英文原文

Title: Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques

Author: Yongshun Lin, Noriko Sato, Sogun Hong, Kenta Nakamura, Elisa A. Ferrante, Zu Xi Yu, Marcus Y. Chen, Daisy S. Nakamura, Xiulan Yang, Randall R. Clevenger, Timothy J. Hunt, Joni L. Taylor, Kenneth R. Jeffries, Karen J. Keeran, Lauren E. Neidig, Atul Mehta, Robin Schwartzbeck, Shiqin Judy Yu, Conor Kelly, Keron Navarengom, Kazuyo Takeda, Stephen S. Adler, Peter L. Choyke, Jizhong Zou, Charles E. Murry, Manfred Boehm, Cynthia E. Dunbar

Issue&Volume: 2024-06-05

Abstract: Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells(iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronicischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinicalchronic myocardial infarctions, all without immunosuppression. Longitudinal positronemission tomography imaging using the sodium/iodide symporter (NIS) reporter generevealed stable grafts for over 6 and 12 months, with no teratoma formation. Histologicalanalyses suggested capability of the transplanted iPSC-CMs to mature and integratewith 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 largeanimal model, addresses concerns regarding neoantigen immunoreactivity of autologousiPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft andmature in human hearts.

DOI: 10.1016/j.stem.2024.05.005

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00182-6