Human Pluripotent Stem Cell-Derived Cardiac Tissue-like Constructs for Repairing the Infarcted Myocardium

Summary: High-purity cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are promising for drug development and myocardial regeneration. However, most hiPSC-derived CMs morphologically and functionally resemble immature rather than adult CMs, which could hamper their application. Here, we obtained high-quality cardiac tissue-like constructs (CTLCs) by cultivating hiPSC-CMs on low-thickness aligned nanofibers made of biodegradable poly(D,L-lactic-co-glycolic acid) polymer. We show that multilayered and elongated CMs could be organized at high density along aligned nanofibers in a simple one-step seeding process, resulting in upregulated cardiac biomarkers and enhanced cardiac functions. When used for drug assessment, CTLCs were much more robust than the 2D conventional control. We also demonstrated the potential of CTLCs for modeling engraftments in vitro and treating myocardial infarction in vivo. Thus, we established a handy framework for cardiac tissue engineering, which holds high potential for pharmaceutical and clinical applications. : Although high-purity cardiomyocytes can be achieved, they are randomly distributed and resemble immature rather than adult CMs. In this article, Liu Li and her colleagues show that 3D and aligned cardiac tissue-like constructs (CTLCs) can be obtained using hPSC-CMs and aligned nanofiber. They also demonstrate the robust drug responses and repair capability of CTLCs in a myocardial infarction model. Keywords: cardiomyocytes, human induced pluripotent stem cells, cardiac tissue-like constructs, myocardial infarction, nanofiber, extracellular recording, drug assessment, coupling, engraftment, arrhythmia