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

  • PDF / 10,662,356 Bytes
  • 15 Pages / 595.276 x 790.866 pts Page_size
  • 37 Downloads / 156 Views

DOWNLOAD

REPORT


RESEARCH

Open Access

Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages Jin Liu1,2†, Xinyu Qiu1†, Yajie Lv1,3†, Chenxi Zheng1, Yan Dong2, Geng Dou1, Bin Zhu1,4, Anqi Liu1, Wei Wang5, Jun Zhou1, Siying Liu1, Shiyu Liu1*, Bo Gao2* and Yan Jin1*

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. (Continued on next page)

* Correspondence: [email protected]; [email protected]; [email protected] † Jin Liu, Xinyu Qiu and Yajie Lv contributed equally to this work. 1 State 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 University, Xi’an 710032, Shaanxi, China 2 State 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 University, Xi’an 710032, Shaanxi, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit lin