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

Abstract Background As 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...

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Main Authors: Jin Liu, Xinyu Qiu, Yajie Lv, Chenxi Zheng, Yan Dong, Geng Dou, Bin Zhu, Anqi Liu, Wei Wang, Jun Zhou, Siying Liu, Shiyu Liu, Bo Gao, Yan Jin
Format: Article
Language:English
Published: BMC 2020-11-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-020-02014-w
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author Jin Liu
Xinyu Qiu
Yajie Lv
Chenxi Zheng
Yan Dong
Geng Dou
Bin Zhu
Anqi Liu
Wei Wang
Jun Zhou
Siying Liu
Shiyu Liu
Bo Gao
Yan Jin
author_facet Jin Liu
Xinyu Qiu
Yajie Lv
Chenxi Zheng
Yan Dong
Geng Dou
Bin Zhu
Anqi Liu
Wei Wang
Jun Zhou
Siying Liu
Shiyu Liu
Bo Gao
Yan Jin
author_sort Jin Liu
collection DOAJ
description Abstract Background As 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. Methods ABs 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. Results We 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. Conclusions Collectively, 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.
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spelling doaj.art-b34587d9491941658c2763cb2db882172022-12-21T21:35:58ZengBMCStem Cell Research & Therapy1757-65122020-11-0111111510.1186/s13287-020-02014-wApoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophagesJin Liu0Xinyu Qiu1Yajie Lv2Chenxi Zheng3Yan Dong4Geng Dou5Bin Zhu6Anqi Liu7Wei Wang8Jun Zhou9Siying Liu10Shiyu Liu11Bo Gao12Yan Jin13State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityAbstract Background As 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. Methods ABs 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. Results We 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. Conclusions Collectively, 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.https://doi.org/10.1186/s13287-020-02014-wApoptotic bodiesExtracellular vesiclesMacrophage polarizationSkin regeneration
spellingShingle Jin Liu
Xinyu Qiu
Yajie Lv
Chenxi Zheng
Yan Dong
Geng Dou
Bin Zhu
Anqi Liu
Wei Wang
Jun Zhou
Siying Liu
Shiyu Liu
Bo Gao
Yan Jin
Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
Stem Cell Research & Therapy
Apoptotic bodies
Extracellular vesicles
Macrophage polarization
Skin regeneration
title Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
title_full Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
title_fullStr Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
title_full_unstemmed Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
title_short Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
title_sort apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
topic Apoptotic bodies
Extracellular vesicles
Macrophage polarization
Skin regeneration
url https://doi.org/10.1186/s13287-020-02014-w
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