Porcine Albumin Elaboration During Perfusion of Transgenic Porcine Livers with Human Blood.
1Department of Surgery, University of Maryland, School of Medicine, Baltimore, MD
2Revivicor, Inc., Blacksburg, VA
Meeting: 2017 American Transplant Congress
Abstract number: B133
Keywords: Liver, Liver metabolism, Xenotransplantation
Session Information
Session Name: Poster Session B: Ischemic Injury and Organ Preservation Session II
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose
In addition to immune barriers, molecular incompatibilities between species are predicted to limit pig liver survival in primate xenotransplantation models. How perfusion with human blood affects synthetic function of genetically modified porcine livers has not previously been described.
Methods
Pig livers were perfused with human blood under physiologic conditions. The phenotype of porcine livers were: α1,3-galactosyl transferase knockout and human membrane cofactor (GalTKO.hCD46, n=8, mean survival time (MST) 390 min); GalTKO.hCD46 plus N-glycolylneuraminic acid knock out (GalTKO.hCD46.Neu5GCKO, n=6, MST 253 min); and GalTKO.hCD46 plus human decay-accelerating factor (hCD55), endothelial protein C receptor (hEPCR), tissue factor pathway inhibitor (hTFPI), and integrin associated protein (hCD47) (GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47, n=6, MST 517 min). Timed blood samples were tested for pig specific albumin via western blot.
Results
Porcine albumin levels increased with time in all experiments (Figure 1). By relative immunofluorescent band intensity, GalTKO.hCD46.Neu5GCKO livers had the highest albumin levels, measured both as total produced, and when controlled for perfusion duration, compared to GalTKO.hCD46 (p= 0.068) and GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47 livers (p=0.04)(Figure 2).
Conclusions
Porcine livers perfused with human blood release albumin over time during perfusion, suggesting preserved synthetic ability. GalTKO.hCD46.Neu5GCKO pig livers demonstrated the most robust albumin production. This suggests that the Neu5GCKO may provide a protective effect on the graft due to decreased human antibody recognition and graft injury.
CITATION INFORMATION: Cimeno A, Powell J, French B, Ayares D, Azimzadeh A, Pierson III R, Barth R, LaMattina J. Porcine Albumin Elaboration During Perfusion of Transgenic Porcine Livers with Human Blood. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Cimeno A, Powell J, French B, Ayares D, Azimzadeh A, III RPierson, Barth R, LaMattina J. Porcine Albumin Elaboration During Perfusion of Transgenic Porcine Livers with Human Blood. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/porcine-albumin-elaboration-during-perfusion-of-transgenic-porcine-livers-with-human-blood/. Accessed November 21, 2024.« Back to 2017 American Transplant Congress