Transplant medicine continues to face a critical shortage of donor organs, with many retrieved grafts discarded due to damage from ischemia, cold storage, and reperfusion. Traditional preservation methods slow this decline but fail to restore the mitochondrial machinery essential for energy production and cell survival. Now, a new review suggests that mitochondrial transplantation during ex vivo perfusion could transform organ preservation from passive storage to active biological reconditioning.
Researchers from Wake Forest University, Brown University, and University Grenoble Alpes reviewed this emerging strategy in Hepatobiliary & Pancreatic Diseases International, published online in October 2025. The article synthesizes preclinical evidence from heart, lung, and kidney models, where delivering healthy mitochondria improved contractility, oxygenation, tissue viability, and metabolic recovery. This approach aims to restore cellular metabolism, limit oxidative injury, and recover function before transplantation, potentially rehabilitating organs currently considered too damaged for use.
The review details findings from donation after circulatory death (DCD) and donation after brain death (DBD) models. In pig hearts, autologous skeletal-muscle mitochondria delivered during normothermic perfusion improved contractile recovery and reduced infarct size by more than 75% in one study. Human platelet-derived mitochondria also entered rat cardiomyocytes, supporting ATP production and cell viability while lowering reactive oxygen species. In lungs, mitochondria added during ex vivo lung perfusion improved oxygenation and reduced vascular resistance, with no signs of acute immune rejection even when sourced from another individual or species. Porcine kidneys showed stimulated metabolic activity and pathways linked to mitochondrial biogenesis after prolonged perfusion.
Mechanistically, transplanted mitochondria may enter cells via endocytosis or membrane fusion, replace damaged organelles, and restore oxidative phosphorylation. However, evidence for liver transplantation remains limited to non-transplant injury models. The proposed clinical framework integrates this therapy across procurement, preservation, and transplantation, rather than at a single step.
The authors emphasize that the goal is not to replace preservation but to transform preservation time into a controlled window for active recovery. They call for shared standards on mitochondrial quality, source, dose, delivery, and safety. "The consistency of benefits across several organs is encouraging," they note, "but the field now needs rigorous protocols."
If validated clinically, mitochondrial transplantation could rescue marginal organs, extend preservation windows, and make long-distance organ sharing more feasible. It could also be integrated into existing machine-perfusion platforms, allowing treatment and viability testing in the same workflow. Before that, researchers must standardize isolation methods, determine the most suitable mitochondrial source, and clarify long-term immune effects. Large-animal studies and carefully designed human trials are essential to establish reproducibility, dosing, and whether short-term metabolic recovery translates into durable graft function.
This review underscores a paradigm shift from merely preserving organs to actively repairing them, offering hope to the thousands of patients awaiting transplants.
