Preclinical Large Animal Porcine Models for Cardiac Regeneration and Its Clinical Translation: Role of hiPSC-Derived Cardiomyocytes

Abstract

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.

Fabrication of heart tubes from iPSC derived cardiomyocytes and human fibrinogen by rotating mold technology

“…Cardiac tissue engineering encompasses established technologies for generating contractile bundle-, patch-or sheet-like constructs [1][2][3] . Recently, based on human iPSC-derived cardiomyocytes (hiPSC-CM), cardiac patches were generated and grafted onto the (left) ventricle of heart failure patients, to support the functional output of the heart in first clinical trials [4][5][6] (https:// www. repai ron.…”

“…de/). However, animal experiments suggest that the functional efficiency and success of cardiac patch transplantation onto the epicardium are challenged by the limited thickness of the constructs, the lack of electromechanical coupling to the host myocardium, and the general issue of immune rejection in a xenogeneic model 6,7 . Other strategies focused on a more holistic approach of "whole organ replacement".…”