The findings, which were published online in the American Journal of Transplantation,
suggest that it’s possible to use the technique of “machine perfusion”
with a newly created cell-free oxygenated solution to expand the number
of high-quality livers available for transplant, thereby shortening
waiting times and reducing patient mortality.
Currently, 20 to 40 percent of donor livers cannot be transplanted
into recipients because oxygen deprivation during storage and transport
in conventional containers can make pre-existing tissue damage worse,
explained senior investigator Paulo Fontes, M.D., UPMC transplant
surgeon, associate professor, Starzl Transplantation Institute,
Department of Surgery, Pitt School of Medicine, and a deputy director of
the McGowan Institute. If the damage is too extensive, the organ cannot
be safely transplanted into a patient.
“Standard practice is to use a method called cold static
preservation, which uses tissue cooling to slow down metabolism with the
aim of reducing the demand for oxygen and thus protecting cells from
death,” Dr. Fontes explained. “In our new system, we pump a special
fluid designed to deliver oxygen to the liver, creating an environment
that supports normal function. The integrity of the cells and vital
metabolic activity is sustained for eventual transplantation of the
organ.”
The research team optimized a machine-perfusion (MP) device that
was developed by Organ Assist, a company in the Netherlands, and added a
fluid with a hemoglobin-oxygen carrier component to deliver high
concentrations of oxygen to the tissue. The liver is immersed in chilled
fluid, which is also pumped through tubes inserted into the organ’s
large blood vessels to effectively oxygenate the tissue.
The team transplanted six pigs with livers that had been kept for
nine hours, roughly the average time between recovery of the organ and
transplantation into a recipient, in the MP system and another six with
organs placed in the standard container.
They found that 100 percent of the pigs who got MP livers survived,
compared to 33 percent of those who received conventionally preserved
organs. The MP livers functioned better, produced more bile and had
higher oxygen levels than their conventional counterparts, and analyses
of multiple biomarkers including inflammatory mediators indicated that
the MP livers had been better preserved.
Also, “it was immediately obvious to us that the pigs who received
MP livers looked much healthier and easily moved around their pens just
hours after they woke up from the surgery,” Dr. Fontes said. “They
didn’t look as ill as the animals treated with standard cold
preservation. It was amazing.”
The data from the studies have been shared with federal regulators,
he added, with the aim of launching a clinical trial to test the system
at UPMC this year.
“This system has great potential to enhance our current standards
for organ preservation, which should translate into more patients
getting a life-saving procedure with potentially better outcomes,” Dr.
Fontes said. “Not only that, we have hopes of a faster recovery because
the liver could be less likely to become injured due to a lack of
oxygen.”
Co-investigators include Roberto Lopez, M.D., Yoram Vodovotz,
Ph.D., Marta Minervini, Ph.D., Victor Scott, M.D., Kyle Soltys, M,D.,
Sruti Shiva, Ph.D., Shirish Paranjpe, Ph.D., David Sadowsky, Derek
Barclay, Ruben Zamora, Ph.D., Donna Stolz, Ph.D., Anthony Demetris,
M.D., George Michalopoulos, M.D., Ph.D., and James Wallis Marsh, M.D.,
all of the University of Pittsburgh; and Arjan van der Plaats, Ph.D.,
of Organ Assist, Groningen, Netherlands.
The study was funded by a charitable gift from Mr. and Mrs. Garcia de Souza, as well as grant DK072146 from the National Institutes of Health.