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Synthetic liver function is detectable in transgenic porcine livers perfused with human blood. Xenotransplantation 2018 Jan;25(1)

Date

10/27/2017

Pubmed ID

29067741

Pubmed Central ID

PMC5809179

DOI

10.1111/xen.12361

Scopus ID

2-s2.0-85041929041 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

In addition to immune barriers, molecular incompatibilities between species are predicted to limit pig liver survival in primate xenotransplantation models. Assessment and measurement of synthetic function of genetically modified porcine livers after ex vivo perfusion with human blood have not previously been described. Eight porcine livers from α1,3-galactosyl transferase knockout and human membrane cofactor (GalTKO.hCD46), six livers from GalTKO.hCD46 and N-glycolylneuraminic acid knockout (GalTKO.hCD46.Neu5GcKO), and six livers from GalTKO.hCD46 with humanized 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) pigs were perfused with human blood under physiologic conditions. Timed blood samples were tested for liver enzymes and for pig-specific albumin production via Western blot. Porcine albumin levels increased with time in all experiments. By densitometry, 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 = .068) and GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47 livers (P = .04). Porcine livers perfused with human blood demonstrated the synthetic ability to produce albumin in all cases. GalTKO.hCD46.Neu5GcKO pig livers demonstrated the most robust albumin production. This suggests that the Neu5GcKO phenotype provides a protective effect on the graft due to decreased human antibody recognition and graft injury.

Author List

Cimeno A, French BM, Powell JM, Phelps C, Ayares D, O'Neill NA, Laird CT, Pierson RN 3rd, Azimzadeh AM, Barth RN, LaMattina JC

Author

Christopher Thomas Laird MD Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Genetically Modified
CD55 Antigens
Extracorporeal Circulation
Gene Knockout Techniques
Graft Survival
Humans
Liver
Lung Transplantation
Membrane Cofactor Protein
Swine
Transplantation, Heterologous