Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model

Abstract

Pluripotent stem cell-derived cardiomyocytes show great promise in regenerating the heart after myocardial infarction; however, several uncertainties exist that must be addressed before clinical trials. One practical issue is graft survival following transplantation. Although a pro-survival cocktail with Matrigel has been shown to enhance graft survival, the use of Matrigel may not be clinically feasible. The purpose of this study was to test whether a hyaluronan-based hydrogel, HyStem, could be a substitute for Matrigel. Human induced pluripotent stem cell-derived cardiomyocytes diluted with HyStem alone, HyStem plus pro-survival factors, or a pro-survival cocktail with Matrigel (PSC/MG), were transplanted into a rat model of acute myocardial infarction. Histological analysis at 4 weeks post transplantation revealed that, among the three groups, recipients of PSC/MG showed the largest graft size. Additionally, the grafted cardiomyocytes in the recipients of PSC/MG had a more matured phenotype compared to those in the other two groups. These findings suggest that further studies will be required to enhance not only graft size, but also the maturation of grafted cardiomyocytes.

A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes

“…In contrast, endothelial cells express extracellular matrices (ECMs; collagens I and III, fibronectin, thrombospondin-4) to increase sarcomere length of hiPSC-CMs (Abecasis et al, 2019). ECMs alone had some effects on enhancing structural and functional maturation of hiPSC-CMs (Chun et al, 2015;Herron et al, 2016;Ogasawara et al, 2017).…”

Maturation strategies and limitations of induced pluripotent stem cell-derived cardiomyocytes

“…Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum [114]. The presence of ECM can also induce the maturation of CMs structure [115].…”

Therapeutic Potential of Pluripotent Stem Cells for Cardiac Repair after Myocardial Infarction

“…One of the main reasons of the death of graft cells is apoptosis by activation of the Jun N-terminal kinase pathway 51) triggered by the loss of matrix attachments, which is known as anoikis. 52) Several cell scaffold materials such as Matri-gel, 23) hyaluronan acid-based extracellular matrix, [53][54][55] and thermosensitive and biodegradable hydrogels 56) have been tested for their ability to control anoikis. Laflamme et al 23) reported that a prosurvival cocktail including Matrigel with hESC-CMs could significantly suppress anoikis and enhance graft survival.…”