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

Mitochondrial transplantation is a promising treatment for many diseases associated with mitochondrial defects or aging; however, a reliable method for mitochondrial transfer remains urgently needed. In this study, we assemble fusogenic and magnet-responsive cells (FMRCs), which are enucleated stem cells loaded with Fe₃O₄ nanoparticles and further incorporated fusogenic vesicular stomatitis virus glycoprotein G (VSV-G). Mitochondrial transplantation from FMRCs via fusion in the presence of a magnetic force restores normal mitotic activity, mitochondrial membrane potential, ROS levels and ATP production in cells subjected to 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 demonstrate that exogenous mitochondria could reside stably and predominantly mitochondrial transplantation stimulates autophagy and thus the clearance of defective endogenous counterparts, resulting in lower mtDNA heteroplasmy. These results suggest that FMRCs are excellent vehicles for mitochondrial transplantation and could be used for the treatment of aging and mitochondria associated diseases.