Fabrication of fusogenic and magnet-responsive cells for transplantation of an intact mitochondrial network

Background Mitochondrial transplantation is a promising cure for many diseases associated with mitochondrial defects or ageing; however, a reliable method for mitochondria transfer is still in urgent need. Method In this study, we assembled fusogenic and magnet-responsive cells (FMRCs), which were enucleated stem cells loaded with Fe ₃ O ₄ nanoparticles and further incorporated with fusogenic vesicular stomatitis virus glycoprotein G (VSV-G). Fusion was carried out in the presence of a magnetic force. Results Mitochondrial transplantation in the presence of a magnetic force via fusion from FMRCs restored normal mitotic activity, mitochondrial membrane potential, ROS levels and ATP production in cells containing partial mtDNA depletion, or in cybrids harboring mtDNA with a 4977-bp deletion. SNP tracing and qPCR analysis of the mitochondrial and nuclear genomes unequivocally demonstrated that exogenous mitochondria were able to reside stably and predominately. Mitochondria transplantation stimulated autophgy and thus the clearance of defective endogenous counterparts, resulted in lower mtDNA heteroplasmy. Conclusion The results suggest that FMRCs is an excellent vehicle for mitochondrial transplantation, which could be applied to the treatment of ageing and mitochondria associated diseases.