Transplant medicine faces a persistent challenge: many donor organs are discarded due to damage from ischemia, cold storage, and reperfusion. Traditional preservation methods slow this decline but do not restore the mitochondrial function essential for cellular energy and survival. A new review suggests that delivering healthy mitochondria during ex vivo perfusion could actively repair organs, turning preservation time into a window for biological reconditioning.
Published in Hepatobiliary & Pancreatic Diseases International (DOI: 10.1016/j.hbpd.2025.10.003), the article synthesizes preclinical evidence from heart, lung, and kidney models. In pig hearts, autologous mitochondria delivered during normothermic perfusion improved contractile recovery and reduced infarct size by more than 75%. Human platelet-derived mitochondria entered rat cardiomyocytes, supporting ATP production and cell viability while lowering reactive oxygen species. In lungs, mitochondria added during ex vivo lung perfusion improved oxygenation and reduced vascular resistance, with no signs of acute immune rejection. Porcine kidneys showed stimulated metabolic activity and mitochondrial biogenesis after prolonged perfusion.
The review's authors, from Wake Forest University, Brown University, and Grenoble Alpes University, emphasize that the goal is not to replace preservation but to enhance it. By integrating mitochondrial transplantation into existing machine-perfusion platforms, clinicians could treat organs and assess viability in the same workflow. This approach could rescue marginal organs that would otherwise be declined, extend preservation times, and make long-distance organ sharing more feasible.
Mechanistically, transplanted mitochondria may enter cells via endocytosis or membrane fusion, replacing damaged organelles and restoring oxidative phosphorylation. However, the field lacks standardized protocols for mitochondrial quality, source, dose, and delivery. The authors call for shared standards and further research to determine whether autologous, allogeneic, or xenogeneic mitochondria are most suitable. They also stress the need for large-animal studies and carefully designed human trials to establish safety and long-term efficacy.
If validated clinically, mitochondrial transplantation could transform organ preservation from passive storage to active recovery, potentially expanding the donor pool and improving transplant outcomes. The review underscores the importance of moving beyond conventional preservation to address the underlying bioenergetic failure in donor organs.
