Mesenchymal stem cells encapsulated in a reactive oxygen species-scavenging and O2-generating injectable hydrogel for myocardial infarction treatment

Abstract

Stem cell especially mesenchymal stem cell (MSC) transplantation is a promising therapeutic strategy for myocardial infarction (MI) repair. However, major obstacles remain due to the poor retention and survival rate of transplanted MSCs in the harmful MI microenvironment (e.g., oxidative stress and hypoxia). Here, a novel injectable hydrogel (RCGel) with dual functions of reactive oxygen species (ROS)-scavenging and O2-generating was employed to encapsulate MSCs for MI treatment. The RCGel encapsulating exhibited anti-ROS protection through inhibiting JNK/p38 apoptosis signaling pathway to improve the viability of MSCs under oxidative stress conditions in vitro. The survival of cardiomyocytes was also improved both in the oxidative stress and hypoxia environments when being co-cultured with MSCs-encapsulated RCGel (MSC/RCGel). The RCGel encapsulating boosted the engraftment of transplanted MSCs in vivo. More viable MSCs endowed with regenerative abilities in the infarcted rat heart along with the ameliorated MI microenvironment (decreased oxidative stress and hypoxia) by the RCGel substantially inhibited cardiac apoptosis, enhanced cardiomyocyte viability, promoted angiogenesis and reduced fibrosis to improve the cardiac functions. The encapsulation of MSCs in RCGel, which exhibits beneficial effects in resisting harsh environments, provides a new way in MI repair and stem cell delivery, and has great potential in cell-based regenerative medicine.