Transplant

April 13, 2023

Process rehabilitates donor livers for transplantation

Vanderbilt research demonstrated that injured human donor livers declined for transplant can be recovered by cross-circulation between the human liver and a xenogeneic host, or animal platform.

Not enough suitable donor livers are available, meaning that patients nationwide die every day while waiting on the transplant list. But a multidisciplinary team from Vanderbilt University Medical Center recently published research that shows promise for increasing the supply of organs by rehabilitating injured organs historically rejected for transplant.

It demonstrated that injured human donor livers declined for transplant can be recovered by cross-circulation between the human liver and a xenogeneic host, or animal platform.

The study, “Xenogeneic cross-circulation for physiologic support and recovery of ex vivo human livers,” appears in the journal Hepatology.

Researchers utilized human livers declined for transplantation and attached them to a xenogeneic platform. Using cross-circulation, they observed the liver over 24 hours of support on the platform.

The research team found the livers began to heal, with improved injury scores after 24 hours on the platform, compared to readings after 12 hours. The physiologic function of the organs was maintained, and they maintained a normal appearance, perfusion and histologic and subcellular architecture.

This rehabilitation technique helps address common reasons why livers are determined unsuitable for transplant — that there is too much fatty tissue or damage from ischemia, for example.

The researchers conclude that the cross-circulation platform could aid the recovery of marginal donor livers to make them viable and could be used as a research tool to develop new strategies for organ recovery and rehabilitation.

The team’s research on livers follows published research from Vanderbilt and Columbia University showing that such a cross-circulation technique with a swine model can rehabilitate human lungs deemed too damaged for transplantation.

“This work is a natural extension of work we demonstrated in human lungs, providing further evidence for the ability to resuscitate rejected human organs using a pig host as a bioreactor,” said the story’s senior author, Matthew Bacchetta MD, MBA, MA, professor of Surgery and adjunct professor of Biomedical Engineering. “It also lays the groundwork for investigating liver injury and recovery in new donor procurement techniques.”

First author Wei Kelly Wu, MD, added, “This platform’s ability to provide durable, multisystem physiologic regulation may be uniquely suited to rehabilitate severely injured organs or study novel therapeutics for organ recovery.”

Although no organs rehabilitated through the technique have yet been transplanted, the procedure could, along with different machine perfusion techniques, eventually increase the limited supply of donor organs, allowing more people the opportunity to receive life-saving liver transplants.

Vanderbilt authors of the study include first author Wu and co-corresponding authors Bacchetta, and Sophoclis Alexopoulos, MD, former associate professor of Surgery and chief of Liver Transplantation at VUMC, now medical director of University of California Davis Transplant Center.