Exosomes derived from pro-inflammatory bone marrow-derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization.

Ruqin Xu,Ming Hu,Mingke Liu,Renjie Chai,Qiong Xu,Xuke Chen,Fangcheng Zhang,Ningning Liu,Wenyi Zhou,Shiming Liu,Bin Liu

doi:10.1111/jcmm.14635

Abstract

Exosomes are served as substitutes for stem cell therapy, playing important roles in mediating heart repair during myocardial infarction injury. Evidence have indicated that lipopolysaccharide (LPS) pre‐conditioning bone marrow‐derived mesenchymal stem cells (BMSCs) and their secreted exosomes promote macrophage polarization and tissue repair in several inflammation diseases; however, it has not been fully elucidated in myocardial infarction (MI). This study aimed to investigate whether LPS‐primed BMSC‐derived exosomes could mediate inflammation and myocardial injury via macrophage polarization after MI. Here, we found that exosomes derived from BMSCs, in both Exo and L‐Exo groups, increased M2 macrophage polarization and decreased M1 macrophage polarization under LPS stimulation, which strongly depressed LPS‐dependent NF‐κB signalling pathway and partly activated the AKT1/AKT2 signalling pathway. Compared with Exo, L‐Exo had superior therapeutic effects on polarizing M2 macrophage in vitro and attenuated the post‐infarction inflammation and cardiomyocyte apoptosis by mediating macrophage polarization in mice MI model. Consequently, we have confidence in the perspective that low concentration of LPS pre‐conditioning BMSC‐derived exosomes may develop into a promising cell‐free treatment strategy for clinical treatment of MI.

Highlights

Numerous studies have indicated that the transplantation of mesenchymal stem cells (MSCs) effectively promotes heart repair and potentially prevents heart remodelling after myocardial infarction (MI).[1-3]
The present study investigated whether LPS‐primed bone marrow‐derived mesenchymal stem cells (BMSCs)‐derived exosomes could mediate inflammation and myocardial injury via macrophage polarization after MI
Exosomes serve as substitutes for BMSCs in cell‐ free therapy, playing important roles in mediating heart repair during myocardial infarction injury.[11,43]

Summary

| INTRODUCTION

Numerous studies have indicated that the transplantation of mesenchymal stem cells (MSCs) effectively promotes heart repair and potentially prevents heart remodelling after myocardial infarction (MI).[1-3]. Exosomes are formed by the inward budding of multivesicular endosomes, are fused with the plasma membrane, and released into the extracellular space to influence the function and physiology of recipient cells.[15] They are the key crosstalk factors in intercellular communication.[16]. An increasing number of studies showed that macrophages play important roles in post‐ infarction inflammation and heart repair.[19]. Upon their different phenotypic and functional plasticities, macrophages are divided into two categories: M1‐like phenotype macrophages (classically activated macrophages) with high expression of CD11b20,21 and iNOS,[22] and elaborate large amounts of pro‐inflammatory cytokine, such as interleukin 6 (IL‐6), interleukin 1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α); the M2‐like phenotype macrophages (alternatively activated macrophages) are characterized by CD206,23 arginase I24 and anti‐inflammatory cytokines (interleukin 10, IL‐10).

| METHODS

Findings

| DISCUSSION