Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration
Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration
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二甲双胍促进间充质干细胞来源的细胞外纳米囊泡的释放并优化椎间盘退变的治疗效果
DOI：
10.1016/j.biomaterials.2021.120850
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发表时间：
2021-05-11
期刊：
影响因子：
14
通讯作者：
Yang, Cao
中科院分区：
文献类型：
--
作者：
Liao, Zhiwei;Li, Shuai;Yang, Cao
细胞外囊泡（EV）是细胞外纳米囊泡，可向细胞递送多种物质并参与细胞通讯。间充质干细胞（MSC）衍生的 EV 被认为是治疗肌肉骨骼退行性疾病（包括椎间盘退变）的方法。然而，有限的产量和不稳定的质量阻碍了EV的临床应用。在本研究中，表明二甲双胍促进 EV 释放并改变 EV 的蛋白质谱。二甲双胍通过自噬相关途径增强 EV 的产生，同时促进突触体相关蛋白 29 的磷酸化。二甲双胍治疗不仅影响 MSC 衍生的 EV 的数量，还影响其质量。蛋白质组学分析表明，二甲双胍可增加参与细胞生长的 EV 的蛋白质含量。结果表明，源自二甲双胍处理的 MSC 的 EV 可在体外和体内改善椎间盘细胞的衰老。总的来说，这些发现证明了二甲双胍在基于 EV 的椎间盘再生中的巨大前景。
Extracellular vesicles (EVs) are extracellular nanovesicles that deliver diverse cargoes to the cell and participate in cell communication. Mesenchymal stem cell (MSCs)-derived EVs are considered a therapeutic approach in musculoskeletal degenerative diseases, including intervertebral disc degeneration. However, limited production yield and unstable quality have impeded the clinical application of EVs. In the present study, it is indicated that metformin promotes EVs release and alters the protein profile of EVs. Metformin enhances EVs production via an autophagy-related pathway, concomitantly with the phosphorylation of synaptosome-associated protein 29. More than quantity, quality of MSCs-derived EVs is influenced by metformin treatment. Proteomics analysis reveals that metformin increases the protein content of EVs involved in cell growth. It is shown that EVs derived from metformin-treated MSCs ameliorate intervertebral disc cells senescence in vitro and in vivo. Collectively, these findings demonstrate the great promise of metformin in EVs-based intervertebral disc regeneration.