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.