Supporting Evidence for Mitochondrial Transfer as Therapy
Bacteria-like mitochondria are the cell's power plants, and they become damaged with age. This damage spirals out to create a small but significant population of cells that export harmful reactive compounds into surrounding tissues and the circulatory system, contributing to a range of age-related conditions. One possible approach to address this issue involves destroying existing damaged mitochondria and replacing them with undamaged versions. Simply introducing new undamaged mitochondria is an easier proposition but probably not sufficient, as the damaged versions overtake cells because they have an advantage in replication: diluting their numbers won't last very long.
Here researchers provide more evidence to show that simply introducing new mitochondria into a tissue environment is probably sufficient to see them taken up into cells and used. This is great news for work on inherited genetic mitochondrial disorders, where supplying new unmutated mitochondria should be a cure, but it is only a part of any potential treatment for the mitochondrial damage of aging based on mitochondrial replacement:
Mitochondria play an essential role in eukaryotes, and mitochondrial dysfunction is implicated in several diseases. Therefore, intercellular mitochondrial transfer has been proposed as a mechanism for cell-based therapy. In addition, internalization of isolated mitochondria cells by simple coincubation was reported to improve mitochondrial function in the recipient cells. However, substantial evidence for internalization of isolated mitochondria is still lacking, and its precise mechanism remains elusive.We tested whether enriched mitochondria can be internalized into cultured human cells by simple coincubation using fluorescence microscopy and flow cytometry. Mitochondria were isolated from endometrial gland-derived mesenchymal cells (EMCs) or EMCs stably expressing mitochondrial-targeted red fluorescent protein (EMCs-DsRed-mito), and enriched by anti-mitochondrial antibody-conjugated microbeads. They were coincubated with isogeneic EMCs stably expressing green fluorescent protein (GFP).
Live fluorescence imaging clearly showed that DsRed-labeled mitochondria accumulated in the cytoplasm of EMCs stably expressing GFP around the nucleus. Flow cytometry confirmed the presence of a distinct population of GFP and DsRed double-positive cells within the recipient cells. In addition, transfer efficiency depended on mitochondrial concentration, indicating that human cells may possess the inherent ability to internalize mitochondria. Therefore, this study supports the application of direct transfer of isogeneic mitochondria as a novel approach for the treatment of diseases associated with mitochondrial dysfunction.