McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
Methods Mol Biol. 2022;2485:191-212. doi: 10.1007/978-1-0716-2261-2_13.
The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has garnered significant attention as a potential means of restoring lost muscle mass and contractile function in injured hearts. Early preclinical work with hPSC-CMs employed rodent models, but the field has recently advanced to transplantation studies in more translationally relevant large animal models including non-human primates and swine. The pig is a particularly attractive model for such studies because the size, structure, and physiology of the porcine heart is very similar to that of humans. The pig model has reasonably high throughput, is readily amenable to clinically available cell delivery methods and imaging modalities and has been used frequently to test the safety and efficacy of new cardiac therapies. Here, we describe methods that were established in our laboratory for the specific purpose of testing hPSC-CM transplantation in a pig model of subacute myocardial infarction, but these same techniques should be broadly applicable to the transepicardial delivery of other biologicals including other candidate cell populations, biomaterials, and/or viral vectors.
人多能干细胞衍生的心肌细胞(hPSC-CMs)的移植作为一种恢复受损心脏中丧失的肌肉质量和收缩功能的潜在方法受到了极大的关注。早期使用 hPSC-CMs 的临床前工作采用了啮齿动物模型,但该领域最近已进展到更具转化相关性的大型动物模型(包括非人类灵长类动物和猪)中的移植研究。猪是此类研究的特别有吸引力的模型,因为猪的心脏大小、结构和生理学与人类非常相似。猪模型具有较高的通量,容易采用临床可用的细胞输送方法和成像方式,并且经常用于测试新的心脏治疗方法的安全性和疗效。在这里,我们描述了我们实验室专门为在亚急性心肌梗死猪模型中测试 hPSC-CM 移植而建立的方法,但这些相同的技术应该广泛适用于其他生物制剂(包括其他候选细胞群、生物材料和/或病毒载体)的经心外膜传递。