Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Attenuate Myocardial Infarction Injury via miR-24-3p-Promoted M2 Macrophage Polarization.

Abstract

Exosomes derived from human umbilical cord mesenchymal stem cells (UMSC-Exos) have shown encouraging effects in regulating inflammation and attenuating myocardial injury. Macrophages are regulated dynamically in response to environmental cues. However, the underlying mechanisms by which UMSC-Exos regulate macrophage polarization are still not well understood. Herein, it is aimed to explore the effects of UMSC-Exos on macrophage polarization and their roles in cardiac repair after myocardial infarction (MI). These results show that UMSC-Exos improve cardiac function by increasing M2 macrophage polarization and reducing excessive inflammation. RNA-sequencing results identify Plcb3 as a key gene involved in UMSC-Exo-facilitated M2 macrophage polarization. Further bioinformatic analysis identifies exosomal miR-24-3p as a potential effector mediating Plcb3 downregulation in macrophages. Increasing miR-24-3p expression in macrophages effectively enhances M2 macrophage polarization by suppressing Plcb3 expression and NF-κB pathway activation in the inflammatory environment. Furthermore, reducing miR-24-3p expression in UMSC-Exos attenuates the effects of UMSC-Exos on M2 macrophage polarization. This study demonstrates that the cardiac therapeutic effects of UMSC-Exos are at least partially through promoting M2 macrophage polarization in an inflammatory microenvironment. Mechanistically, exosomal miR-24-3p is found to inhibit Plcb3 expression and NF-κB pathway activation to promote M2 macrophage polarization.