Mitochondrial transplantation

Mitochondrial transplantation involves the direct transfer of intact, metabolically functional mitochondria — isolated from autologous or allogeneic tissue — into ischaemic or otherwise bioenergetically compromised cells or organs to supplement or replace dysfunctional mitochondria. The best-documented clinical context is paediatric cardiac surgery: McCully and colleagues (Boston Children's Hospital) reported in a preliminary 2017 JTCVS communication that autologous mitochondria injected into ischaemia-injured myocardium improved ventricular function in children with postcardiotomy ECMO-dependent cardiogenic shock; a larger 2020 JTCVS case series (n=24) showed 80% successful ECMO separation versus 29% in controls. This application is now in early clinical study (NCT02851758). Mechanistic proposals include import via clathrin-mediated endocytosis, macropinocytosis, and direct membrane fusion, though the dominant uptake pathway and long-term mitochondrial survival in recipient cells remain under investigation. Application to aging is hypothetical: in preclinical models, intravenous mitochondrial infusion has been reported to improve muscle function and cognitive markers in aged rodents, but the route, source tissue, dosing, and safety profile for systemic aging applications are not established, and no approved indication for aging exists.