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

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

  • Int J Oral Sci. 2023 Jan 16;15(1):7. doi: 10.1038/s41368-022-00205-0.
Qingyuan Ye # 1 2,  Xinyu Qiu # 3,  Jinjin Wang 4,  Boya Xu 5,  Yuting Su 6,  Chenxi Zheng 1,  Linyuan Gui 1,  Lu Yu 1,  Huijuan Kuang 1,  Huan Liu 1 7,  Xiaoning He 1,  Zhiwei Ma 4,  Qintao Wang 8,  Yan Jin 9
Affiliations

Affiliations

  • 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.
  • 8 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. wangqintao@aliyun.com.
  • 9 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. yanjin@fmmu.edu.cn.
  • # Contributed equally.
PMID: 36646698 DOI: 10.1038/s41368-022-00205-0
Abstract

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-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that Apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the Apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs 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 ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs 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.

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