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

Rui Bai,Lei Tian,Huiliang Liu,Yi Li,Yujie Wei,Zhiqiang Liu,Jiao Zhang,Zhigeng Jin

doi:10.1155/2019/6708435

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.

Highlights

Ischemic cardiovascular disease (CVD) is one of the major causes of morbidity and mortality worldwide [1, 2]
Selection of scaffolds and seeding cells was crucial to achieve a satisfied therapeutic outcome, e.g., a scaffold suitable to an ischemic microenvironment and a seeding cell with potent cardiomyogenic potential were important for MI
Heart-derived extracellular matrix (ECM) hydrogel was selected as a scaffold to facilitate brown adipose-derived stem cells (BADSCs) transplantation in MI for the first time

Summary

Introduction

Ischemic cardiovascular disease (CVD) is one of the major causes of morbidity and mortality worldwide [1, 2]. Exogenous regeneration with stem cells was proposed for myocardial repair and widely investigated [5, 6]. Transplanted stem cells may promote myocardial repair through a paracrine effect or regeneration. Due to the limited regeneration from exogenous cells, clinical practice benefited little from laboratory achievements in stem cell-based therapy of MI [7,8,9]. It is vital to explore a type of seeding cells with high cardiomyogenic potentials and minimize the adverse influence of an engrafted microenvironment, so as to improve stem cell-based myocardial repair and further the clinical application in the future

Methods

Results

Conclusion