MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts  

作　　者：Qingyuan Ye Xinyu Qiu Jinjin Wang Boya Xu Yuting Su Chenxi Zheng Linyuan Gui Lu Yu Huijuan Kuang Huan Liu Xiaoning He Zhiwei Ma Qintao Wang Yan Jin 

机构地区：[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,Air Force Medical University,Xi’an,China [2]State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology,Digital Dentistry Center,School of Stomatology,Air Force Medical University,Xi’an,China [3]State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral Diseases,Department of Preventive Dentistry,School of Stomatology,Air Force Medical University,Xi’an,China [4]State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture,Department of Periodontology,School of Stomatology,Air Force Medical University,Xi’an,China [5]State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Oral Diseases,Department of Prosthodontics,School of Stomatology,Air Force Medical University,Xi’an,China [6]Aerospace Clinical Medical Center,School of Aerospace Medicine,Air Force Medical University,Xi’an,China [7]Department of Otolaryngology Head and Neck Surgery,Peking University Third Hospital,Beijing,China

出　　处：《International Journal of Oral Science》2023年第1期63-75,共13页国际口腔科学杂志（英文版）

基　　金：supported by the National Key Research and Development Program of China(2021YFA1100600);National Natural Science Foundation of China(82170955,32101096,and 32100953);Shaanxi Provincial Key Research and Development Plan Project(2022SF-095);the Youth Talent Training Project for School of Stomatology in Fourth Military Medical University(2020QNYC01)。

摘　　要：Severe muscle injury is hard to heal and always results in a poor prognosis.Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine,however,whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown.Herein,we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells(MSCs-Apo EVs)to treat cardiotoxin induced tibialis anterior(TA)injury and found that MSCs-Apo EVs promoted muscles regeneration and increased the proportion of multinucleated cells.Besides that,we also found that apoptosis was synchronized during myoblasts fusion and MSCs-Apo EVs promoted the apoptosis ratio as well as the fusion index of myoblasts.Furthermore,we revealed that MSCs-Apo EVs increased the relative level of creatine during myoblasts fusion,which was released via activated Pannexin 1 channel.Moreover,we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived Apo EVs(Myo-Apo EVs)instead of apoptotic myoblasts,and creatine was the pivotal metabolite involved in myoblasts fusion.Collectively,our findings firstly revealed that MSCs-Apo EVs can promote muscle regeneration and elucidated that the new function of Apo EVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel,which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

关 键 词：APO extracellular RELEASE 

分 类 号：R685[医药卫生—骨科学]