Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages

Jin Liu,Anqi Liu,Shiyu Liu,Bo Gao,Xinyu Qiu,Yajie Lv,Yan Jin,Geng Dou,Wei Wang,Chenxi Zheng,Jun Zhou,Siying Liu,Yan Dong,Bin Zhu

doi:10.1186/s13287-020-02014-w

Abstract

BackgroundAs the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects.MethodsABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro.ResultsWe found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process.ConclusionsCollectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.

Highlights

The skin is the largest organ of the human body which serves as the first defense line to the external environment, so that it is liable to different kinds of injuries
Collectively, our study demonstrated that transplanted mesenchymal stem cells (MSCs) promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an antiinflammatory phenotype that plays a crucial role in the tissue repair process
Transplanted MSCs promoted cutaneous wound healing after transplantation Bone marrow mesenchymal stem cells (BMMSCs) were isolated from 8-week-old female wild type (WT) C57BL/6 mice, and the second passage was used for characterization

Summary

Introduction

The skin is the largest organ of the human body which serves as the first defense line to the external environment, so that it is liable to different kinds of injuries. Various strategies have been explored, among which exogenous mesenchymal stem cells (MSCs) showed a great potential [2]. We previously observed extensive apoptosis of transplanted MSCs in a short time after transplantation in a rabbit skin wound healing model and found that apoptosis has an important role in the activation of the inflammatory regulatory abilities of MSCs [9]. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. We observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects

Methods

Results

Discussion

Conclusion