MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts / 国际口腔科学杂志·英文版

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.

Influence of TNF-α on the immunomodulatory property of laryngeal mucosa mesenchymal stromal cells′ / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the effect of tumor necrosis factor-alpha(TNF-α)on the immunoregulatory capacity of laryngeal mucosal mesenchymal stromal cells (LM-MSCs) and its potential molecular mechanism, and provide a theoretical basis for the study of chronic laryngitis.@*Methods@#LM-MSCs were separated from epiglottal mucosa. The LM-MSCs cells were directly co-cultured with T cells in vitro to detect the immunomodulatory property of LM-MSCs. After long-term stimulation with inflammatory factors TNF-α in vitro, the differences were compared in the immunomodulatory ability of LM-MSCs between normal LM-MSCs and TNF-α stimulated LM-MSCs. The expression of general control non-repressed protein5(GCN5), FAS, FASL in normal LM-MSCs and TNF-α stimulated LM-MSCs was detected by Western blot and quantitative real-time RT-PCR(RT-qPCR).@*Results@#After chronic stimulation of TNF-α, the RNA relative expression of GCN5 was 0.31±0.03 (3 days) and 0.53±0.06 (7 days) compared with control group, showing significant difference (F=13.45, P<0.05). The percentage of LM-MSC-induced T cell apoptosis was 6.27%±0.81% (3 days) and 4.99%±0.52% (7 days) in chronic stimulation group compared with control group 10.02%±1.02%. There is a significant difference among these groups (F=11.13, P<0.05). Moreover, the ability of LM-MSCs to induce T cell apoptosis is regulated by GCN5.@*Conclusion@#With the chronic stimulation of TNF-α, the expression of GCN5 in LM-MSCs is decreased, thus impairing its immunoregulatory capacity.

Rescue of recipient MSC functions and remission of recipient osteoporosis by donor MSC-derived exosomes through transfer of miR-26a / 实用口腔医学杂志

Objective:To explore mechanisms underlying the rescuing effects of transplanted mesenchymal stem cells (MSCs) derived exosomes on estrogen-deficient osteoporosis.Methods:Mouse estrogen-deficient osteoporosis model was constructed in 12 female C57BL6/J rats and the exosome release was regulated by siRNA.Osteogenic induction,alizarin red staining and qPCR were performed to evaluate the effects of exosomes on recipient MSC functions.The miR-26a mimics and inhibitors and qPCR were used to explore the mechanisms underlying exosome-mediated functional rescue of recipient MSCs.Results:Donor MSCs alleviated estrogen-deficient osteoporosis via exosome release,and the alleviated osteoporosis by exosomes rescued the recipient MSC functions were observed.Moreover,the rescued recipient MSC functions by exosomes transferred miR-26a were found.Conclusion:Donor MSC-derived exosomes may rescue MSC functions and may remit osteoporosis of the recipient through transfering miR-26a.