DURHAM, NC – A new review published in Hepatobiliary & Pancreatic Diseases International suggests that transplanting healthy mitochondria into donor organs during machine perfusion could transform organ preservation from passive storage into active repair. The strategy, which involves delivering mitochondria to organs ex vivo, aims to restore cellular energy production, reduce oxidative injury, and improve function before transplantation. If validated, this approach could help rescue organs currently deemed too damaged for use and expand the donor pool.
The review, led 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. In pig hearts, autologous skeletal-muscle mitochondria delivered through the coronary circulation during normothermic perfusion improved contractile recovery and reduced oxygen use, with one study reporting a reduction in infarct size by more than 75%. Human platelet-derived mitochondria 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 sourced from another individual or even another species did not trigger acute immune rejection in preclinical experiments. In porcine kidneys, autologous mitochondria stimulated metabolic activity and pathways linked to mitochondrial biogenesis and energy metabolism after prolonged perfusion.
The mechanism behind these benefits appears to involve mitochondrial entry into cells via endocytosis or membrane fusion, where they replace damaged organelles, restore oxidative phosphorylation, and rebalance redox and inflammatory signaling. However, evidence for liver transplantation remains limited, with only related non-transplant injury models studied to date.
The authors emphasize that the goal is not to replace current preservation methods but to transform the preservation period into a controlled window for active recovery. "The central idea is to stop treating donor organs as tissues that can only be protected from further decline," they stated. "Mitochondria could give transplant teams a practical way to address energy failure while an organ is already connected to a perfusion system."
The consistency of benefits across several organs is encouraging, but the field needs shared standards for mitochondrial quality, source, dose, delivery, and safety. "The aim is not to replace preservation," the authors added, "but to transform preservation time into a controlled window for active recovery."
If clinically validated, mitochondrial transplantation could help rescue marginal hearts, lungs, kidneys, and possibly livers that would otherwise be declined. It could also extend safe preservation windows, making long-distance organ sharing more feasible. The therapy could 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.
This review provides a comprehensive overview of the current state of mitochondrial transplantation in organ preservation, highlighting its potential to address the critical shortage of donor organs. As the technology progresses, it may become a key tool in the effort to rehabilitate organs previously considered unusable, ultimately improving outcomes for patients on transplant waiting lists.
