Mitochondrial Transplantation During Machine Perfusion Could Recondition Damaged Donor Organs

Organ transplantation faces a persistent crisis: too few donor organs and too many that are discarded due to damage from ischemia, cold storage, and reperfusion. A novel strategy aims to change this by delivering healthy mitochondria to organs during ex vivo perfusion, shifting the goal from merely slowing deterioration to actively repairing cellular damage. A review published in Hepatobiliary & Pancreatic Diseases International synthesizes preclinical evidence suggesting that mitochondrial transplantation could restore energy production, reduce oxidative injury, and improve organ function before transplantation.

The review, authored by researchers from Wake Forest University, Wake Forest School of Medicine, Brown University, University Grenoble Alpes, and Grenoble Alpes University Hospital, examines studies in heart, lung, and kidney models. In pig hearts, autologous mitochondria delivered via coronary circulation during normothermic perfusion improved contractile recovery and reduced infarct size by more than 75%. Human platelet-derived mitochondria entered rat cardiomyocytes, sustaining ATP production and cell viability while lowering reactive oxygen species. In lungs, mitochondria added during ex vivo lung perfusion improved oxygenation and reduced pulmonary vascular resistance, with no acute immune rejection even when mitochondria came from another individual or species. In porcine kidneys, autologous mitochondria stimulated metabolic activity and pathways linked to mitochondrial biogenesis.

The proposed mechanism involves mitochondria entering cells via endocytosis or membrane fusion, replacing damaged organelles, and restoring oxidative phosphorylation and redox balance. While liver transplantation evidence remains limited to non-transplant injury models, the authors propose integrating this therapy across procurement, preservation, and transplantation. They argue that the current focus on maintaining organs should shift to active recovery, with machine perfusion providing a controlled window for treatment.

The implications are significant. If validated clinically, mitochondrial transplantation could rescue marginal organs, extend preservation times, and enable long-distance organ sharing. It could be integrated into existing perfusion platforms, allowing simultaneous treatment and viability testing. However, the authors emphasize the need for standardized protocols for mitochondrial isolation, quality control, dosage, and delivery. They also call for large-animal studies and carefully designed human trials to confirm reproducibility, safety, and long-term outcomes.

The review, published with DOI: 10.1016/j.hbpd.2025.10.003, is available online. The research was supported by institutions including the First Affiliated Hospital of Zhejiang University School of Medicine, which owns the journal.