A new preservation system that pumps cooled, oxygen-rich fluid into donor livers not only keeps the organs in excellent condition for as long as nine hours before transplantation, but also leads to dramatically better liver function and increases survival of recipients, according to a series of animal studies by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine. The system could be tested with transplant patients at UPMC later this year.
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.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.
Contact: Anita Srikameswaran
Contact: Jennifer Yates
Anita Srikameswaran | EurekAlert!
Visualizing gene expression with MRI
23.12.2016 | California Institute of Technology
Illuminating cancer: Researchers invent a pH threshold sensor to improve cancer surgery
21.12.2016 | UT Southwestern Medical Center
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Trade Fair News
16.01.2017 | Automotive Engineering
16.01.2017 | Life Sciences