by Matt Batcheldor
A multidisciplinary team from Vanderbilt University Medical Center is studying whether injured human donor livers declined for transplant can be recovered by cross-circulation between the human liver and a xenogeneic host.
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. Though no organs rehabilitated through the technique have yet been transplanted, the procedure could eventually increase the limited supply of donor organs, allowing more people the opportunity to receive life-saving transplants, said Matthew Bacchetta, MD, MBA, MA, professor of Surgery and adjunct professor of Biomedical Engineering.
VUMC general surgery resident Wei Kelly Wu, MD, is working on the project with Bacchetta and Sophoclis Alexopoulos, MD, associate professor of Surgery and chief of Liver Transplantation at VUMC.
VUMC’s groundbreaking research comes as two genetically modified pig organs were reported to have been transplanted into humans in January. In September 2021, surgeons at NYU Langone Health attached a genetically modified pig kidney to a brain-dead donor, and it worked normally.
Surgeons at University of Alabama at Birmingham recently reported they had also transplanted genetically modified pig kidneys into a brain-dead donor, and remarkably, a man received a heart from a genetically modified pig at the University of Maryland Medical Center.
Those experimental techniques are called xenotransplant — transplanting animal organs into humans. What VUMC is studying is the use of xenogeneic cross circulation to rehabilitate rejected human organs with severe but reversible injuries using a pig as a physiologic bioreactor. Bacchetta said that, once perfected, the xenogeneic technique could provide a more acceptable pathway for increasing organ availability than xenotransplantation because it would not be affected by chronic rejection issues associated with animal organs.
“For us, the boundary of xenotransplant has been crossed, very publicly, and this is an open field now,” Bacchetta said. “The xenogeneic platform is now potentially an even more acceptable pathway for regenerating organs and increasing organ availability for patients, both lung and liver, and possibly other organs.”
Wu said the team has demonstrated the technique on four livers thus far, and early results are very promising.
“The liver maintains its function for a full 24 hours,” Wu said. “And globally, it looks like liver at the end of the experiment. It uses energy and nutrients. It makes bile. It clears waste. It seems to do everything that a liver is supposed to do when we decide to stop.”
Alexopoulos said the technique especially holds promise for livers, because, unlike lungs, they naturally can regenerate and repair themselves.
“We believe that we can take a liver and we just need to provide a healthy environment for it to be able to repair itself and regenerate,” he said.
The rehabilitation technique would address common reasons why livers are determined unsuitable for transplant — that there is too much fatty tissue and/or are physically damaged, with lacerations, for example.
Wu said the team is looking to extend the support of the livers beyond 24 hours as it explores other therapies to rehabilitate them. The earlier experiments on lungs demonstrated the ability to maintain and rehabilitate them for up to four days, she noted.
The stakes of such research are high. In 2019, the most recently reported data available, 9.26% of livers procured by surgeons in the U.S. were discarded, Wu noted. That’s approximately 900 to 1,000 livers annually. Many more donors are turned down before even an attempt at procurement.
“Globally, in the field of transplantation, the shortage of suitable donor organs is a huge issue, despite the field having come very far in the last three or four decades,” Wu said.
“This couldn’t have come at a better time because of the other stories in the news — two major accomplishments within the span of a month. It’s almost like an arms race. Really, the future is now.”
