Transplant medicine faces a persistent challenge: many donor organs are discarded due to damage from ischemia, cold storage, and reperfusion. While machine perfusion has improved preservation, it largely maintains organs rather than repairing them. A new review suggests that delivering healthy mitochondria during perfusion could shift the paradigm from passive preservation to active reconditioning.
Researchers from Wake Forest University, Wake Forest School of Medicine, Brown University, University Grenoble Alpes, and Grenoble Alpes University Hospital synthesized preclinical evidence from heart, lung, and kidney models, published in Hepatobiliary & Pancreatic Diseases International (DOI:10.1016/j.hbpd.2025.10.003). The review, available online October 14, 2025, and in the June 2026 issue, outlines how mitochondrial transplantation may restore cellular energy production, reduce oxidative injury, and improve graft function before implantation.
The concept addresses a fundamental issue: when an organ is removed, its mitochondria—the powerhouses of cells—suffer from oxygen deprivation, leading to energy failure and cell death. By introducing healthy mitochondria during ex vivo perfusion, the hope is to repair cellular metabolism and enhance viability. The review details encouraging results from animal models. In pig hearts, autologous mitochondria delivered during normothermic perfusion improved contractile recovery and reduced infarct size by over 75% in one study. Human platelet-derived mitochondria entered rat cardiomyocytes and supported ATP production while lowering reactive oxygen species. In lungs, mitochondrial addition during ex vivo lung perfusion improved oxygenation and reduced vascular resistance. Porcine kidneys showed increased metabolic activity and mitochondrial biogenesis pathways.
Mechanistically, transplanted mitochondria may enter cells via endocytosis or membrane fusion, replacing damaged organelles and restoring oxidative phosphorylation. The approach is particularly relevant for organs from donation after circulatory death (DCD) and donation after brain death (DBD), which are more susceptible to ischemic injury.
The authors stress that this is not about replacing preservation, but about transforming the preservation period into a therapeutic window. "The central idea is to stop treating donor organs as tissues that can only be protected from further decline," they noted. "Mitochondria could instead give transplant teams a practical way to address energy failure while an organ is already connected to a perfusion system."
While the consistency of benefits across organs is promising, significant hurdles remain. Standardization of mitochondrial isolation, characterization, and dosing is needed. Questions about the optimal source—autologous, allogeneic, or xenogeneic—and long-term immune effects must be resolved. Large-animal studies and human trials are essential to confirm safety and efficacy.
If validated, mitochondrial transplantation could help rescue marginal organs, extend preservation times, and facilitate long-distance organ sharing. It could be integrated into existing machine-perfusion platforms, allowing simultaneous treatment and viability testing. This approach has the potential to expand the donor pool and improve outcomes for patients awaiting transplants.
