In the high-stakes world of organ transplantation, the race against time after a donor organ is removed may soon have a new ally: mitochondrial transplantation. A comprehensive review published in Hepatobiliary & Pancreatic Diseases International presents preclinical evidence that delivering healthy mitochondria during ex vivo perfusion could shift the focus from merely slowing organ deterioration to actively repairing damage. This approach, if validated clinically, could help rescue organs that are currently deemed too damaged for transplantation, thereby expanding the limited donor pool and potentially saving more lives.
Transplant medicine is constrained by a critical shortage of donor organs, and many retrieved grafts are discarded due to cellular damage caused by ischemia, cold storage, and reperfusion. Conventional preservation methods slow this decline but do not restore the mitochondrial machinery essential for energy production and cell survival. Machine perfusion offers a window for intervention, yet most systems are designed to maintain rather than rebuild organ 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, explores how mitochondrial transplantation could turn this preservation window into an active recovery period.
The review synthesizes findings from preclinical heart, lung, and kidney models. In pig hearts, autologous mitochondria delivered during normothermic perfusion improved contractile recovery, reduced oxygen consumption, and in one study, decreased infarct size by over 75%. 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 (EVLP) improved oxygenation, reduced pulmonary vascular resistance, and dampened inflammation, even when sourced from another individual or species, without signs of acute immune rejection. Porcine kidneys showed enhanced metabolic activity and mitochondrial biogenesis after prolonged perfusion with autologous mitochondria.
The proposed mechanism involves transplanted mitochondria entering cells via endocytosis or membrane fusion, replacing damaged organelles, and restoring oxidative phosphorylation and redox signaling. While liver transplantation evidence is limited to non-transplant injury models, the authors suggest that this therapy could be integrated across procurement, preservation, and transplantation stages.
The key implication is that donor organs could be biologically reconditioned, not just passively stored. "The central idea is to stop treating donor organs as tissues that can only be protected from further decline," the authors 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 organs is encouraging, but the field needs standardized protocols for mitochondrial quality, source, dose, and safety.
If clinical trials succeed, mitochondrial transplantation could rescue marginal hearts, lungs, kidneys, and possibly livers, extend safe preservation times, and make long-distance organ sharing more feasible. It could also be seamlessly integrated into existing machine-perfusion platforms, allowing simultaneous treatment and viability testing. However, researchers must first standardize isolation and characterization methods, determine the optimal 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.
The review is published in Hepatobiliary & Pancreatic Diseases International with the DOI: 10.1016/j.hbpd.2025.10.003. The original source can be accessed at https://doi.org/10.1016/j.hbpd.2025.10.003.
