Transplant medicine faces a persistent challenge: many donor organs are discarded because ischemia, cold storage, and reperfusion cause rapid cellular damage. Conventional preservation methods slow this decline but fail to restore the mitochondrial machinery that powers cellular energy production and regulates survival, inflammation, and oxidative balance. A new review published in Hepatobiliary & Pancreatic Diseases International suggests that mitochondrial transplantation during machine perfusion could change the paradigm from passive preservation to active reconditioning.
The review, authored by researchers from Wake Forest University, Wake Forest School of Medicine, Brown University, University Grenoble Alpes, and Grenoble Alpes University Hospital, synthesizes preclinical evidence from heart, lung, and kidney models. The findings indicate that delivering healthy mitochondria during ex vivo perfusion can restore cellular metabolism, limit oxidative injury, and improve organ function before transplantation. In pig hearts, autologous skeletal-muscle mitochondria delivered via the coronary circulation during normothermic perfusion improved contractile recovery and reduced oxygen use; one study reported a more than 75% reduction in infarct size. Human platelet-derived mitochondria also entered rat cardiomyocytes, supporting ATP production and cell viability while lowering reactive oxygen species.
In lung models, mitochondria added during ex vivo lung perfusion improved oxygenation, reduced pulmonary vascular resistance, and dampened inflammatory signals, even when sourced from another individual or species, without signs of acute immune rejection. Porcine kidneys treated with autologous mitochondria showed enhanced metabolic activity and pathways linked to mitochondrial biogenesis after prolonged perfusion. Mechanistically, transplanted mitochondria may enter cells through endocytosis or membrane fusion, replace damaged organelles, and rebalance redox and inflammatory signaling. However, evidence for liver transplantation remains limited to non-transplant injury models.
The authors argue that the central idea is to stop viewing donor organs as tissues that can only be protected from further decline. Instead, mitochondria could provide a practical way to address energy failure while the organ is already connected to a perfusion system. The consistency of benefits across several organs is encouraging, but the field now needs shared standards for mitochondrial quality, source, dose, delivery, and safety. The aim is not to replace preservation but to transform preservation time into a controlled window for active recovery.
If validated clinically, mitochondrial transplantation could help rescue marginal hearts, lungs, kidneys, and possibly livers that would otherwise be declined, while extending safe preservation windows and making long-distance organ sharing more feasible. It could also be integrated into existing machine-perfusion platforms, allowing treatment and viability testing to occur in the same workflow. Before that can happen, researchers must standardize isolation and characterization methods, determine whether mitochondria from the same individual, another individual, or another species are most suitable, and clarify their long-term fate and immune effects. Large-animal studies and carefully designed human trials will be essential to establish reproducibility, dosing, safety, and whether short-term metabolic recovery translates into durable graft function.
The review, published with DOI 10.1016/j.hbpd.2025.10.003, provides a comprehensive overview of the current state of mitochondrial transplantation in organ preservation. As research progresses, this innovative approach could significantly expand the donor pool and improve outcomes for transplant recipients worldwide.
