Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, 56 Lingyuanxi Road, Guangzhou, 510055, People's Republic of China.
J Nanobiotechnology. 2024 Sep 5;22(1):543. doi: 10.1186/s12951-024-02818-5.
Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. In vitro expansion is necessary to provide clinical-grade quantities of mesenchymal stem cells; however, it has been reported to cause replicative senescence and undefined dysfunction in mesenchymal stem cells. Quality control assessments of in vitro expansion have rarely been addressed in ongoing trials. Young small extracellular vesicles from the remnant pulp of human exfoliated deciduous teeth stem cells have demonstrated therapeutic potential for diverse diseases. However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines.
We demonstrated that mitochondrial structural disruption precedes cellular dysfunction during bone marrow-derived mesenchymal stem cell replication, indicating mitochondrial parameters as quality assessment indicators of mesenchymal stem cells. Dynamin-related protein 1-mediated mitochondrial dynamism is an upstream regulator of replicative senescence-induced dysfunction in bone marrow-derived mesenchymal stem cells. We observed that the application of young small extracellular vesicles could rescue the pluripotency dissolution, immunoregulatory capacities, and therapeutic effects of replicative senescent bone marrow-derived mesenchymal stem cells. Mechanistically, young small extracellular vesicles could promote Dynamin-related protein 1 translocation from the cytoplasm to the mitochondria and remodel mitochondrial disruption during replication history.
Our findings show that Dynamin-related protein 1-mediated mitochondrial disruption is associated with the replication history of bone marrow-derived mesenchymal stem cells. Young small extracellular vesicles from human exfoliated deciduous teeth stem cells alleviate replicative senescence by promoting Dynamin-related protein 1 translocation onto the mitochondria, providing evidence for a potential rejuvenation strategy.
人类间充质干细胞在再生医学中受到关注，并且正在许多临床试验中进行测试。体外扩增是提供临床级数量间充质干细胞所必需的；然而，据报道，它会导致间充质干细胞的复制衰老和功能不明。正在进行的试验很少涉及对体外扩增的质量控制评估。来自人类脱落乳牙残余牙髓的年轻小细胞外囊泡已被证明对多种疾病具有治疗潜力。然而，目前尚不清楚年轻小细胞外囊泡是否可以逆转与衰老相关的衰退。
我们证明了骨髓间充质干细胞复制过程中线粒体结构的破坏先于细胞功能障碍，表明线粒体参数作为间充质干细胞质量评估指标。与复制衰老诱导的骨髓间充质干细胞功能障碍相关的动力相关蛋白 1介导的线粒体动力学是一种上游调节剂。我们观察到，年轻小细胞外囊泡的应用可以挽救复制衰老的骨髓间充质干细胞的多能性溶解、免疫调节能力和治疗效果。从机制上讲，年轻小细胞外囊泡可以促进动力相关蛋白 1从细胞质向线粒体的易位，并在复制历史期间重塑线粒体破坏。
我们的研究结果表明，动力相关蛋白 1介导的线粒体破坏与骨髓间充质干细胞的复制历史有关。来自人类脱落乳牙干细胞的年轻小细胞外囊泡通过促进动力相关蛋白 1易位到线粒体来减轻复制衰老，为潜在的年轻化策略提供了证据。
