Combining ECM Hydrogels of Cardiac Bioactivity with Stem Cells of High Cardiomyogenic Potential for Myocardial Repair

Abstract

Tissue engineering exploring the combination of scaffolds and seeding cells was proposed as a promising strategy for myocardial repair. However, the therapeutic outcomes varied greatly due to different selection of scaffolds and seeding cells. Herein, the potential of combining bioactive extracellular matrix (ECM) hydrogels and high cardiomyogenic seeding cells was explored for myocardial repair in vitro and in vivo. Temperature-sensitive ECM hydrogels were prepared from decellularized rat hearts, and cardiomyogenic seeding cells were isolated from brown adipose (brown adipose-derived stem cells (BADSCs)). The in vitro studies demonstrated that ECM hydrogel significantly supported the proliferation and cardiomyogenic differentiation of BADSCs. Importantly, the function and maturation of BADSC-derived cardiomyocytes were also promoted as evidenced by Ca2+ transient’s measurement and protein marker expression. After myocardial transplantation, the combination of BADSCs and ECM hydrogels significantly preserved cardiac function and chamber geometry compared with BADSCs or ECM hydrogels alone. Meanwhile, the ECM hydrogel also enhanced BADSC engraftment and myocardial regeneration in vivo. These results indicated that heart-derived ECM hydrogels exerted significant influence on the fate of cardiomyogenic cells toward benefiting myocardial repair, which may explain the enhanced stem cell therapy by the scaffold. Collectively, it indicated that the combination of ECM hydrogel and the cardiomyogenic cells may represent a promising strategy for cardiac tissue engineering.