April 6, 2023

System repairs donor lungs for transplantation

A Vanderbilt team has discovered that donor lungs rejected for transplant can be repaired using cross-circulation with a xenogeneic host.

Only 20% of donor lungs are in sufficient condition for transplantation, which means that many people die every day while waiting on the transplant list. Discovering new ways to increase the supply of donor lungs is an urgent problem and is desperately needed to save lives of patients with chronic lung disease.

A Vanderbilt team has discovered that donor lungs rejected for transplant can be repaired using cross-circulation with a xenogeneic (swine) host.

In this system, a declined human donor lung is connected via catheters to a live swine, which serves as a bioreactor. The swine provides critical physiologic and hormonal support needed to support the recovery of the lung.

Until now, the exposure of the human lung to animal blood has had unknown immunologic interactions, raising concerns of negative consequences after a potential future transplantation into a human. But a new Vanderbilt-led study, which characterized immunologic interactions, found no clinical signs of acute rejection while on the xenogeneic platform. The study, “Immune characterization of a xenogeneic human lung cross-circulation support system,” was recently published in the journal Science Advances.

The first author is Wei Kelly Wu, MD, general surgery resident at VUMC, and corresponding authors are Matthew Bacchetta, MD, MBA, professor of Surgery, and Ciara Shaver, MD, PhD, assistant professor of Medicine.

This study shows that swine immune cells and immunoglobulins infiltrate the human lung during cross-circulation. “We demonstrate that a porcine xenogeneic XC (cross-circulation) system is capable of supporting the viability and physiologic improvement of human donor lungs despite significant and complex human-swine immunologic interactions,” the study states.

The current standard of care for marginal donor lungs is ex vivo lung perfusion (EVLP), a mechanical support system that can preserve lungs for up to six hours but has limited means to rehabilitate lungs.

Vanderbilt has demonstrated that a lung that failed to improve on EVLP could be rehabilitated using the xenogeneic platform.

The xenogeneic platform offers scientists two immediate research pathways, Bacchetta has said. First, it offers a new option for transplanting lungs previously considered too damaged for transplant. Secondly, the xenogeneic platform allows lungs to be preserved to test further therapeutic interventions as well as investigations in drug discovery, testing and delivery.

“This immunologic characterization paves the way forward for using this platform to support not only marginal donor lungs, but other declined organs as well,” Wu said.

The next steps are to determine what happens if these lungs are re-exposed to human blood, prior to consideration of transplantation into humans. This current study lays the foundation translational studies, which Shaver and Bacchetta are working on.

If ongoing studies are successful, the cross-circulation platform has the potential to eliminate the shortage of donor lungs and may be used to recover additional human organs and tissue.