MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing

Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound h...

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Main Authors: Xiaoning He, Zhiwei Dong, Yina Cao, Han Wang, Shiyu Liu, Li Liao, Yan Jin, Lin Yuan, Bei Li
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/7132708
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author Xiaoning He
Zhiwei Dong
Yina Cao
Han Wang
Shiyu Liu
Li Liao
Yan Jin
Lin Yuan
Bei Li
author_facet Xiaoning He
Zhiwei Dong
Yina Cao
Han Wang
Shiyu Liu
Li Liao
Yan Jin
Lin Yuan
Bei Li
author_sort Xiaoning He
collection DOAJ
description Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing. In vitro coculture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA.
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institution Kabale University
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series Stem Cells International
spelling doaj-art-f0e0f31b56fb43828f9b17597ec164f22025-02-03T01:33:23ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/71327087132708MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound HealingXiaoning He0Zhiwei Dong1Yina Cao2Han Wang3Shiyu Liu4Li Liao5Yan Jin6Lin Yuan7Bei Li8State 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, Fourth Military Medical University, Xi’an, Shaanxi 710032, ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi 710032, ChinaDepartment of Stomatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, ChinaDepartment of Stomatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, ChinaState 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, Fourth Military Medical University, Xi’an, Shaanxi 710032, ChinaState 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, Fourth Military Medical University, Xi’an, Shaanxi 710032, ChinaState 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, Fourth Military Medical University, Xi’an, Shaanxi 710032, ChinaDepartment of Stomatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, ChinaState 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, Fourth Military Medical University, Xi’an, Shaanxi 710032, ChinaMesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing. In vitro coculture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA.http://dx.doi.org/10.1155/2019/7132708
spellingShingle Xiaoning He
Zhiwei Dong
Yina Cao
Han Wang
Shiyu Liu
Li Liao
Yan Jin
Lin Yuan
Bei Li
MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
Stem Cells International
title MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
title_full MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
title_fullStr MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
title_full_unstemmed MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
title_short MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
title_sort msc derived exosome promotes m2 polarization and enhances cutaneous wound healing
url http://dx.doi.org/10.1155/2019/7132708
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