Stanford Cardiovascular Institute, Stanford, CA 94305-5454, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA 94305, USA.
Departments of Medicine and Pharmacology, University of California, San Diego, CA 92093, USA.
Stem Cell Reports. 2018 Feb 13;10(2):422-435. doi: 10.1016/j.stemcr.2018.01.002. Epub 2018 Feb 1.
Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 10 NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9-14/group) at 4 days after 60-min coronary artery occlusion-reperfusion. Cardiac function and left ventricular remodeling were similarly improved in both iPSC-CM-treated groups. To mimic the ischemic environment in the infarcted heart, both cultured NHP and human iPSC-CMs underwent 24-hr hypoxia in vitro. Both cells and media were collected, and similarities in transcriptomic as well as metabolomic profiles were noted between both groups. In conclusion, both NHP and human iPSC-CMs confer similar cardioprotection in a rodent myocardial infarction model through relatively similar mechanisms via promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis.
非人灵长类动物（NHPs）可作为一种类似人类的模型，用于研究使用诱导多能干细胞衍生的心肌细胞（iPSC-CMs）的细胞治疗。然而，NHP 和人类 iPSC-CMs 的疗效在机制上是否相似尚不清楚。为了研究这一点，RNU 大鼠在冠状动脉闭塞再灌注后 4 天接受 1×10 的 NHPs 或人类 iPSC-CMs 或相同数量的相应成纤维细胞或 PBS 对照（每组 n=9-14）的心肌内注射。在两种 iPSC-CM 治疗组中，心脏功能和左心室重构均得到类似改善。为了模拟梗死心脏中的缺血环境，体外培养的 NHPs 和人类 iPSC-CMs 均经历了 24 小时的缺氧。收集细胞和培养基，并注意到两组之间在转录组和代谢组学图谱上具有相似性。总之，NHP 和人类 iPSC-CMs 通过促进细胞存活、血管生成以及抑制肥大和纤维化，通过相对相似的机制在啮齿动物心肌梗死模型中提供类似的心脏保护作用。
