Huang Xiaona, Gao Hui, He Juncai, Ge Lingling, Cha Zhe, Gong Hong, Lin Xi, Li Huiting, Tang Yongping, Jiang Dan, Fan Xiaotang, Xu Haiwei
Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
iScience. 2024 Jun 20;27(7):110309. doi: 10.1016/j.isci.2024.110309. eCollection 2024 Jul 19.
Mitochondrial dysfunction and Müller cells gliosis are significant pathological characteristics of retinal degeneration (RD) and causing blinding. Stem cell therapy is a promising treatment for RD, the recently accepted therapeutic mechanism is cell fusion induced materials transfer. However, whether materials including mitochondrial transfer between grafted stem cells and recipient's cells contribute to suppressing gliosis and mechanism are unclear. In present study, we demonstrated that bone marrow mesenchymal stem cells (BMSCs) transferred mitochondria to Müller cells by cell fusion and tunneling nanotubes. BMSCs-derived mitochondria (BMSCs-mito) were integrated into mitochondrial network of Müller cells, improving mitochondrial function, reducing oxidative stress and gliosis, which protected visual function partially in the degenerative rat retina. RNA sequencing analysis revealed that BMSCs-mito increased mitochondrial DNA (mtDNA) content and facilitated mitochondrial fusion in damaged Müller cells. It suggests that mitochondrial transfer from BMSCs remodels Müller cells metabolism and suppresses gliosis; thus, delaying the degenerative progression of RD.
线粒体功能障碍和 Müller 细胞胶质增生是视网膜变性（RD）的重要病理特征，可导致失明。干细胞疗法是一种有前景的 RD 治疗方法，目前被认可的治疗机制是细胞融合诱导的物质转移。然而，包括移植干细胞与受体细胞之间线粒体转移在内的物质是否有助于抑制胶质增生及其机制尚不清楚。在本研究中，我们证明骨髓间充质干细胞（BMSCs）通过细胞融合和隧道纳米管将线粒体转移至 Müller 细胞。BMSCs 来源的线粒体（BMSCs - mito）被整合到 Müller 细胞的线粒体网络中，改善线粒体功能，减轻氧化应激和胶质增生，从而在退行性大鼠视网膜中部分保护视觉功能。RNA 测序分析显示，BMSCs - mito 增加了受损 Müller 细胞中线粒体 DNA（mtDNA）的含量并促进线粒体融合。这表明 BMSCs 的线粒体转移重塑了 Müller 细胞的代谢并抑制了胶质增生，从而延缓了 RD 的退行性进展。
