Yingying Peng, Tingting Zhao, Shuxuan Rong, Shuqing Yang, Wei Teng, Yunyi Xie, Yan Wang
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However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378612/pdf/","citationCount":"0","resultStr":"{\"title\":\"Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics.\",\"authors\":\"Yingying Peng, Tingting Zhao, Shuxuan Rong, Shuqing Yang, Wei Teng, Yunyi Xie, Yan Wang\",\"doi\":\"10.1186/s12951-024-02818-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. 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引用次数: 0
摘要
背景:人类间充质干细胞已引起再生医学的兴趣,并正在许多临床试验中进行测试。要提供临床级数量的间充质干细胞,体外扩增是必要的;但有报道称,体外扩增会导致间充质干细胞复制衰老和未确定的功能障碍。正在进行的试验很少涉及体外扩增的质量控制评估。从人类脱落牙齿残髓中提取的幼小细胞外囊泡干细胞已证明对多种疾病具有治疗潜力。然而,年轻的细胞外小泡是否能逆转衰老相关的衰退仍不清楚:结果:我们证明,在骨髓间充质干细胞复制过程中,线粒体结构破坏先于细胞功能障碍,这表明线粒体参数是间充质干细胞的质量评估指标。Dynamin-related protein 1介导的线粒体活力是骨髓间充质干细胞复制衰老诱导功能障碍的上游调节因子。我们观察到,应用幼小细胞外囊泡可以挽救复制性衰老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。从机理上讲,年轻的细胞外小泡可促进Dynamin相关蛋白1从细胞质转位到线粒体,并在复制过程中重塑线粒体的破坏:我们的研究结果表明,Dynamin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。来自人类脱落牙齿干细胞的幼小细胞外囊泡通过促进Dynamin相关蛋白1在线粒体上的转位,缓解了复制衰老,为一种潜在的年轻化策略提供了证据。
Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics.
Background: 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.
Results: 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.
Conclusions: 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.
期刊介绍:
Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.