Hyaluronate supports hESC-cardiomyocyte cell therapy for cardiac regeneration after acute myocardial infarction

Abstract

Introduction: Enormous progress has been made in cardiac regeneration using human embryonic stem cell-derived cardiomyocyte (hESC-CM) grafts in pre-clinical trials. However, the rate of cell survival has remained very low due to anoikis after transplantation into the heart as single cells. Numerous solutions have been proposed to improve cell survival, and one of these strategies is to co-transplant biocompatible materials or hydrogels with the hESC-CMs. Methods: In our study, we screened various combinations of biomaterials that could promote anoikis resistance and improve hESC-CM survival upon co-transplantation and promote cardiac functional recovery. We injected different combinations of Matrigel, alginate and hyaluronate with hESC-CM suspensions into the myocardium of rat models with myocardial infarction (MI). Results: Our results showed that the group treated with a combination of hyaluronate and hESC-CMs had the lowest arrhythmia rates when stimulated with programmed electrical stimulation. While all three combinations of hydrogel-hESC-CM treatments improved rat cardiac function compared with the saline control group, the combination with hyaluronate most significantly reduced pathological changes from left ventricular remodelling and improved both left ventricular function and left ventricular ejection fraction by 28 days post-infarction. Conclusion: Hence, we concluded that hyaluronate-hESC-CM is a superior combination therapy for promoting cardiac regeneration after myocardial infarction.