Adhesion-Assisted Antioxidant-Engineered Mesenchymal Stromal Cells for Enhanced Cardiac Repair in Myocardial Infarction.

Abstract

Mesenchymal stromal cell (MSC) therapy holds great promise for treating myocardial infarction (MI). However, the inflammatory and reactive oxygen species (ROS)-rich environment in infarcted myocardium challenges MSC survival, limiting its therapeutic impact. In this study, we demonstrate that chemical modification of MSCs with anti-VCAM1 and polydopamine (PD) significantly enhances MSC survival and promotes cardiac repair. Anti-VCAM1 modification facilitates MSC adhesion to inflamed tissue, ensuring MSC retention in the injured myocardium, while PD scavenges ROS surrounding MSCs, creating a conducive environment for cell transplantation. Our data indicate that chemically engineered MSCs effectively disrupt the inflammation-ROS cycle and modulate inflammation-related immune responses, thus improving MI microenvironments. Single-cell RNA sequencing of rat hearts reveals that treatment with engineered MSCs inhibits cardiac fibrosis by suppressing HB-EGF-EGFR signaling between anti-inflammatory macrophages and activated fibrillates. Ultimately, engineered MSCs demonstrate superior therapeutic efficacy in a rat model of MI. This study presents a straightforward, safe, and efficient chemical method for enhancing MSC therapy.