As the demand for transplantable organs continues to outpace supply, a new review suggests that mitochondrial transplantation during machine perfusion could help repair damaged donor organs, potentially expanding the donor pool. The review, published in Hepatobiliary & Pancreatic Diseases International (DOI: 10.1016/j.hbpd.2025.10.003), synthesizes preclinical evidence from heart, lung, and kidney models, indicating that delivering healthy mitochondria to organs during ex vivo perfusion can improve function and viability.
Conventional organ preservation relies on slowing deterioration, but it does not reverse the cellular damage caused by ischemia and reperfusion. Mitochondria, the powerhouses of cells, are crucial for energy production and regulating oxidative stress and inflammation. During organ retrieval and storage, mitochondrial function is compromised, leading to energy failure and cell death. The review proposes that introducing viable mitochondria during machine perfusion could restore cellular metabolism and actively repair tissue damage.
In preclinical studies, mitochondrial transplantation has shown encouraging results across multiple organ types. In pig hearts, delivering autologous skeletal-muscle mitochondria during normothermic perfusion improved contractile recovery and reduced infarct size by more than 75% in one study. Similarly, human platelet-derived mitochondria entered rat heart cells and supported ATP production and cell viability while reducing reactive oxygen species. In lung models, mitochondria added during ex vivo lung perfusion improved oxygenation and reduced inflammatory markers, with benefits observed even when mitochondria were sourced from another individual or species. Porcine kidney studies showed that autologous mitochondria stimulated metabolic activity and pathways associated with mitochondrial biogenesis.
The mechanistic basis for these benefits involves the uptake of mitochondria by cells, which can replace damaged organelles and restore oxidative phosphorylation. However, the review notes that evidence for liver transplantation remains limited, and significant technical and safety questions must be addressed before clinical use.
The authors emphasize that this approach could shift transplantation from passive preservation to active reconditioning. “The central idea is to stop treating donor organs as tissues that can only be protected from further decline,” they said. “Mitochondria could instead give transplant teams a practical way to address energy failure while an organ is already connected to a perfusion system.”
If validated clinically, mitochondrial transplantation could rescue marginal organs that would otherwise be discarded, extend safe preservation times, and facilitate long-distance organ sharing. It could also be integrated into existing machine perfusion platforms, allowing treatment and viability assessment in the same workflow. However, researchers must first standardize methods for mitochondrial isolation and characterization, determine the optimal source (autologous, allogeneic, or xenogeneic), and clarify long-term immune effects. Large-animal studies and carefully designed human trials are essential to establish reproducibility, dosing, safety, and whether early metabolic recovery translates into durable graft function.
The review brings together evidence from researchers at Wake Forest University, Brown University, University Grenoble Alpes, and other institutions, providing a comprehensive overview of this emerging field. The findings suggest that mitochondrial transplantation during machine perfusion could be a transformative approach to organ preservation, offering new hope for patients awaiting transplants.
