As the demand for transplantable organs continues to outpace supply, a novel strategy aims to turn the tide by actively repairing donor organs rather than merely preserving them. Researchers have reviewed the emerging field of mitochondrial transplantation during machine perfusion, a technique that could restore cellular energy production and reduce injury in organs deemed too damaged for transplantation.
When an organ is removed from a donor, it undergoes ischemia, cold storage, and reperfusion, which can rapidly impair cellular function. Conventional preservation methods slow this decline but fail to restore the mitochondria, the powerhouses of the cell that regulate energy production, inflammation, and oxidative balance. Machine perfusion offers a window for intervention, yet current systems primarily maintain organs rather than rebuild their function. This new approach seeks to change that by introducing healthy mitochondria during perfusion, actively repairing cellular metabolism and limiting oxidative injury.
A review published in Hepatobiliary & Pancreatic Diseases International (DOI: 10.1016/j.hbpd.2025.10.003) consolidates preclinical evidence from heart, lung, and kidney models. In pig hearts, delivery of autologous skeletal-muscle mitochondria during normothermic perfusion improved contractile recovery, reduced oxygen consumption, and, in one study, cut infarct size by more than 75%. Human platelet-derived mitochondria also entered rat cardiomyocytes, supporting membrane potential, ATP production, and cell viability while lowering reactive oxygen species.
In lung models, mitochondria added during ex vivo lung perfusion (EVLP) improved oxygenation, reduced pulmonary vascular resistance, and dampened inflammatory signals. Notably, mitochondria from another individual or even another species produced benefits without signs of acute immune rejection. In porcine kidneys, autologous mitochondria stimulated metabolic activity and pathways linked to mitochondrial biogenesis and energy metabolism after prolonged perfusion.
The proposed mechanism involves mitochondria entering cells through endocytosis or membrane fusion, replacing damaged organelles, restoring oxidative phosphorylation, and rebalancing redox and inflammatory signaling. However, evidence for liver transplantation remains limited to related non-transplant injury models, and the review calls for more research in this area.
The authors emphasize that the goal is not to replace preservation but to transform preservation time into a controlled window for active recovery. "The consistency of benefits across several organs is encouraging," they note, "but the field now needs shared standards for mitochondrial quality, source, dose, delivery, and safety."
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 clinical use, researchers must standardize isolation and characterization methods, determine the most suitable mitochondrial source (autologous, allogeneic, or xenogeneic), and clarify 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, authored by researchers from Wake Forest University, Wake Forest School of Medicine, Brown University, University Grenoble Alpes, and Grenoble Alpes University Hospital, was published online on October 14, 2025, and is included in the journal's June 2026 issue. It synthesizes evidence from donation after circulatory death (DCD) and donation after brain death (DBD) models, providing a roadmap for future research.
For more details, the original article can be accessed via the DOI: 10.1016/j.hbpd.2025.10.003.
