Mesenchymal stem cell mitochondrial transfer effectively protects Leber's Hereditary Optic Neuropathy (LHON) mutant cells from mitochondrial damage.

Leber's Hereditary Optic Neuropathy (LHON) is the most prevalent mitochondrial inherited disorder, primarily caused by primary mitochondrial mutations. Clinically, LHON is characterized by degeneration of optic nerves that leads to acute or subacute sudden or painless central vision loss. Currently no effective treatment has been established for LHON. Recent studies have highlighted the significance of intercellular mitochondrial transfer, which facilitates communication between cells and presents a novel therapeutic avenue. In this study, we investigated the formation of tunnelling nanotubes (TNTs) and the subsequent mitochondrial transfer between Bone Marrow Mesenchymal Stem Cells (BM-MSCs) and LHON ND4 mutant cells within the coculture system. Our findings demonstrated that mitochondrial transfer from BM-MSCs to LHON mutant cells via TNTs effectively rescued the mutant LHON cells by reducing apoptosis, restoring mitochondrial membrane potential and reducing reactive oxygen species (ROS) generation. These results provide compelling evidence of cell-cell communication between mesenchymal stem cells and LHON mutant cells, indicating a potential regenerative capacity through the reduction in mitochondrial mutation load. This study would help to implement further research in this area for the protective effect of mitochondria transfer and future cell-based treatment approaches for LHON.