The pioneering research led by Paulo Fontes, MD, FACS (pictured), UPMC transplant surgeon, associate professor, Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, and a deputy director of the McGowan Institute for Regenerative Medicine, in the development of a new hemoglobin-based oxygen carrier (HBOC) for organ and tissue preservation in combination with machine perfusion (MP) has been selected as a 2016 TechConnect Innovation Awardee. The TechConnect Innovation Awards selects the top early-stage innovations from around the world through an industry-review process of the top 15% of annually submitted technologies into the TechConnect National Innovation Summit. Rankings are based on the potential positive impact the submitted technology will have on a specific industry sector
A new HBOC molecule is being developed by VirTech Bio (VTB) LLC, Beverly, Massachusetts, under the leadership of W. Richard Light, PhD, in collaboration with faculty members from Ohio State University, Columbus, Ohio. Dr. Light, a leading HBOC scientist, has been collaborating with Dr. Fontes for several years in the development of this new approach to promote effective ex vivo oxygenation over an extended period of time. They initially developed and patented this technology in 2012, after a series of proof-of-concept pre-clinical experiments in liver transplantation at the McGowan Institute. They have further expanded this application for a discarded human liver and subsequently for vascularized composite allografts (VCA). The MP/HBOC technology is intended to enhance organ and tissue preservation prior to transplantation and it is expected to have a positive impact in clinical transplantation in the near future. Organ preservation is currently based on cold storage (CS), where the organs remain hypothermic and anoxic for a limited period of time. CS has a direct negative impact on organ quality and on the time and the distances imposed by the current system of organ allocation
The McGowan Institute team has signed a Corporate Research Agreement with VTB, which is intended to advance this technology through the current regulatory pathway for medical devices once an investigational device exemption (IDE) has been granted by the FDA. The group has published their original manuscript in the American Journal of Transplantation
in 2015. Seven additional studies have been recently accepted to be presented at the American Transplant Congress, June 2016, Boston, Massachusetts, which includes some intriguing new findings about the ability of the MP/HBOC system to induce a hibernation-like state in swine liver allografts preserved at 21°C over a 9-hour period.
The MP/HBOC technology has been expanded into pre-clinical experiments with VCA and successfully presented at the European Society of Organ Transplantation in 2015. The VCA studies were initially sponsored by the Department of Defense (DOD) as a way to successfully complete the initial proof-of-concept experiments. Further developments with a full limb transplant model are currently underway at the Institute of Surgical Research, San Antonio Medical Center, San Antonio, Texas, under the leadership of Lieutenant Colonel Michael Davis, MD, FACS, and in collaboration with deputy director Vijay Gorantla, MD, PhD, both McGowan Institute for Regenerative Medicine affiliated faculty members. The same beneficial impact of effective ex vivo oxygenation in subsequent tissue regeneration seen extensively in liver allografts has been further reproduced in VCA. These studies are aimed to provide better therapeutic options for limb rescue, replantation, and transplantation in the near future.
Further collaborations are also underway with McGowan Institute for Regenerative Medicine faculty member Yoram Vodovotz, PhD, and his team, who have shown a beneficial effect of ex vivo oxygenation in decreasing inflammatory networks when compared to CS. Dr. Vodovotz has introduced a novel analytic approach for the MP/HBOC ex vivo system by performing principal component analysis and several forms of dynamic network analysis with inflammatory markers sampled during liver preservation. This computational biology approach has helped identify potentially novel anti-inflammatory effects of this novel organ preservation system.
Machine perfusion is already a clinical reality in kidney and lung transplantation, but still costly with some of the new devices used under normothermic (37°C) conditions and with red blood cells as their primary oxygen carrier component.
The TechConnect awards will be presented during the TechConnect-National Innovation Summit, Washington, D.C., May 22-25, 2016.
Illustration: TechConnect Innovation Awards/McGowan Institute for Regenerative Medicine.
2016 TechConnect Innovation Awards
Bio: Dr. Paulo Fontes
Bio: Dr. Michael Davis
Bio: Dr. Vijay Gorantla
Bio: Dr. Yoram Vodovotz
Abstract (American Journal of Transplantation; 01/22/15.)