During the American Transplant Congress, Seattle, WA (May 20, 2013),
McGowan Institute for Regenerative Medicine
affiliated faculty member Paulo Fontes, MD (pictured), assistant professor of surgery at the University of Pittsburgh School of Medicine, described the ground breaking results from a study conducted by a multidisciplinary team who designed and assessed the effectiveness of a system to oxygenate harvested livers with a perfusion system so that the condition of the liver can be maintained for an extended period before implantation.
The team of investigators included participants from the Starzl Transplantation Institute, Department of Surgery, and the McGowan Institute for Regenerative Medicine-University of Pittsburgh—including McGowan affiliated faculty member Anthony Demetris, MD, professor of pathology and director, Division of Transplantation Pathology at the Starzl Transplantation Institute—and the University of Pittsburgh Medical Center.
The team has successfully developed a new modality for organ preservation in a series of pre-clinical studies using a porcine model. The team has pioneered the use of a newly developed hemoglobin-based-oxygen-carrier (HBOC) solution in combination with machine perfusion (MP) at subnormothermic conditions (21°C) for liver preservation prior to transplantation (Provisional Patent Application No. 61/713,284). These experiments compared MP with the current standard of care for organ preservation which is currently based on cold storage (CS), where the organs stay immersed in preservation solutions under hypothermic conditions (4°C) without oxygenation or flow of the preservation fluid through the organ.
In the preclinical study, the team was able to obtain 100% survival with excellent clinical outcomes in a series of liver transplants (n=6) performed after 9 hours of preservation of the harvested liver. This challenging liver transplant porcine model was previously shown as having 70-100% mortality after preservation with the CS method. Statistical analysis has shown a significant benefit (p<0.004) for the MP approach when more than 16 variables were analyzed. These encouraging results were based on extensive analyses of tissue and perfusate samples, which include histology, immunohistochemistry, electron microscopy, tissue oxygenation, in addition to mitochondrial function and micro-array for genetic analysis.
This has been an investigator-initiated initiative from the team which will be followed by a pre-IDE (investigational device exemption) submission to the FDA in the next few months. The group intends to pursue subsequent clinical trials with this newly developed technology as a way to enhance organ utilization and transplant outcomes. The current discard rate for livers is around 20% overall and 50% for donors after cardiac death in some regions. The team believes that the utilization of donated livers can be enhanced through the utilization of these technologies.
These experiments have been performed in collaboration with OPK Biotech, Cambridge, MA (HBOC solution) and Organ Assist, Groningen Netherlands (MP device). This project has been fully sponsored by a charitable grant from the VGS Foundation.
Illustration: McGowan Institute for Regenerative Medicine.
Bio: Dr. Paulo Fontes
Bio: Dr. Anthony Demetris
Abstract (American Transplant Congress, Seattle, WA, May 18-22, 2013, Abstract # 285, presented May 20, 2013.)