Mitochondrial transfer between BMSCs and Müller promotes mitochondrial fusion and suppresses gliosis in degenerative retina

骨髓间充质干细胞与穆勒细胞之间的线粒体转移可促进线粒体融合并抑制退行性视网膜的胶质增生。

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作者:Xiaona Huang ,Luodan A ,Hui Gao ,Juncai He ,Lingling Ge ,Zhe Cha ,Hong Gong ,Xi Lin ,Huiting Li ,Yongping Tang ,Dan Jiang ,Xiaotang Fan ,Haiwei Xu

Abstract

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. Keywords: cell biology; sensory neuroscience.

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