Researchers are exploring a novel approach to repair damaged donor organs by transplanting healthy mitochondria during machine perfusion, a technique that could significantly expand the pool of transplantable organs. A comprehensive review published in Hepatobiliary & Pancreatic Diseases International examines the potential of this strategy to transform organ preservation from passive storage to active biological reconditioning.
The review, conducted by scientists from Wake Forest University, Brown University, and Grenoble Alpes University, synthesizes preclinical evidence from heart, lung, and kidney models. In these studies, mitochondrial delivery during ex vivo perfusion improved key functional outcomes such as cardiac contractility, pulmonary oxygenation, and renal metabolic activity. For instance, in pig hearts, autologous mitochondria delivered through the coronary circulation reduced infarct size by over 75% and enhanced contractile recovery. Similarly, in lungs, adding mitochondria during ex vivo lung perfusion improved oxygenation and reduced inflammatory markers, while in kidneys, autologous mitochondria stimulated metabolic pathways linked to energy production.
The rationale behind this approach is that ischemia, cold storage, and reperfusion cause significant cellular damage by impairing mitochondrial function, which is critical for energy production and cell survival. Current preservation methods only slow this decline but do not restore the damaged mitochondria. Machine perfusion offers a window of opportunity to treat organs outside the body, and mitochondrial transplantation could capitalize on this by delivering healthy mitochondria to repair cellular metabolism and limit oxidative injury.
Mechanistically, transplanted mitochondria are thought to enter cells via endocytosis or membrane fusion, replace damaged organelles, and restore oxidative phosphorylation, thereby rebalancing redox and inflammatory signaling. The review notes that mitochondria sourced from the same individual, another individual, or even another species have shown benefits without acute immune rejection in preclinical experiments.
However, the strategy remains experimental, and several challenges must be addressed before clinical application. These include standardizing mitochondrial isolation and characterization, determining the optimal source (autologous, allogeneic, or xenogeneic), and clarifying the long-term fate and immune effects of transplanted mitochondria. Large-animal studies and carefully designed human trials are needed to establish safety, dosing, and reproducibility.
If validated, mitochondrial transplantation could help rescue marginal organs that are currently discarded due to concerns about viability. This would not only enlarge the donor pool but also extend safe preservation times, making long-distance organ sharing more feasible. The approach could be integrated into existing machine-perfusion platforms, allowing treatment and viability testing in the same workflow.
The authors emphasize that the goal is not to replace preservation but to transform preservation time into a controlled window for active recovery. As they state, the central idea is to stop treating donor organs as tissues that can only be protected from further decline. Instead, mitochondria could provide a practical way to address energy failure while the organ is already connected to a perfusion system.
The review is published under DOI:10.1016/j.hbpd.2025.10.003 and is available online at https://doi.org/10.1016/j.hbpd.2025.10.003. The journal, Hepatobiliary & Pancreatic Diseases International, is owned by the First Affiliated Hospital, Zhejiang University School of Medicine, and publishes peer-reviewed research on hepatobiliary and pancreatic diseases.
