Preclinical Large Animal Porcine Models for Cardiac Regeneration and Its Clinical Translation: Role of hiPSC-Derived Cardiomyocytes.
Preclinical Large Animal Porcine Models for Cardiac Regeneration and Its Clinical Translation: Role of hiPSC-Derived Cardiomyocytes.
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心肌梗死（MI）是由于冠状动脉阻塞导致左心室心肌缺血和心肌细胞坏死而发生的。垂死的心脏组织被纤维瘢痕组织取代，导致心肌收缩力下降，从而影响心肌的功能能力。治疗，如支架置入术，心脏搭桥术或移植是有益的，但有许多限制，并可能减少整体预期寿命由于相关的并发症。近年来，随着人类诱导多能干细胞（hiPSC）的出现，使用基于细胞的方法治疗MI的新途径已成为心脏再生的潜力。虽然hiPSC及其衍生的分化细胞是有希望的候选者，但由于临床前再现性差，其用于临床应用的可转化性受到阻碍。从小鼠到非人灵长类动物，MI的各种临床前动物模型已被用于心血管研究以模拟人类MI。因此，一个全面的文献综述是必不可少的，以阐明影响大动物模型的可重复性和可翻译性的因素。在这篇综述文章中，我们讨论了可用于研究干细胞移植在心血管应用中的不同动物模型，主要集中在高度可翻译的猪MI模型上。
Myocardial Infarction (MI) occurs due to a blockage in the coronary artery resulting in ischemia and necrosis of cardiomyocytes in the left ventricular heart muscle. The dying cardiac tissue is replaced with fibrous scar tissue, causing a decrease in myocardial contractility and thus affecting the functional capacity of the myocardium. Treatments, such as stent placements, cardiac bypasses, or transplants are beneficial but with many limitations, and may decrease the overall life expectancy due to related complications. In recent years, with the advent of human induced pluripotent stem cells (hiPSCs), newer avenues using cell-based approaches for the treatment of MI have emerged as a potential for cardiac regeneration. While hiPSCs and their derived differentiated cells are promising candidates, their translatability for clinical applications has been hindered due to poor preclinical reproducibility. Various preclinical animal models for MI, ranging from mice to non-human primates, have been adopted in cardiovascular research to mimic MI in humans. Therefore, a comprehensive literature review was essential to elucidate the factors affecting the reproducibility and translatability of large animal models. In this review article, we have discussed different animal models available for studying stem-cell transplantation in cardiovascular applications, mainly focusing on the highly translatable porcine MI model.
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