Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biomaterials. 2021 Jul;274:120850. doi: 10.1016/j.biomaterials.2021.120850. Epub 2021 May 6.
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.
细胞外囊泡 (EVs) 是一种细胞外的纳米囊泡，可将各种货物递送到细胞内，并参与细胞通讯。间充质干细胞 (MSCs) 衍生的 EVs 被认为是治疗肌肉骨骼退行性疾病的一种方法，包括椎间盘退行性变。然而，产量有限和质量不稳定阻碍了 EVs 的临床应用。本研究表明，二甲双胍促进 EVs 的释放，并改变 EVs 的蛋白质谱。二甲双胍通过自噬相关途径增强 EVs 的产生，同时磷酸化突触相关蛋白 29。二甲双胍处理不仅影响 EVs 的产生数量，还影响其质量。蛋白质组学分析显示，二甲双胍增加了 EVs 中涉及细胞生长的蛋白质含量。研究表明，来自二甲双胍处理的 MSC 的 EVs 可改善体外和体内椎间盘细胞衰老。总之，这些发现表明二甲双胍在基于 EVs 的椎间盘再生方面具有巨大的潜力。
