In:
Xenotransplantation, Wiley, Vol. 25, No. 1 ( 2018-01)
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 (Gal TKO . hCD 46), six livers from Gal TKO . hCD 46 and N‐glycolylneuraminic acid knockout (Gal TKO . hCD 46.Neu5Gc KO ), and six livers from Gal TKO . hCD 46 with humanized decay‐accelerating factor ( hCD 55), endothelial protein C receptor ( hEPCR ), tissue factor pathway inhibitor ( hTFPI ), and integrin‐associated protein ( hCD 47) (Gal TKO . hCD 46. hCD 55. hEPCR . hTFPI . hCD 47) 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, Gal TKO . hCD 46.Neu5Gc KO livers had the highest albumin levels, measured both as total produced, and when controlled for perfusion duration, compared to Gal TKO . hCD 46 ( P = .068) and Gal TKO . hCD 46. hCD 55. hEPCR . hTFPI . hCD 47 livers ( P = .04). Porcine livers perfused with human blood demonstrated the synthetic ability to produce albumin in all cases. Gal TKO . hCD 46.Neu5Gc KO pig livers demonstrated the most robust albumin production. This suggests that the Neu5Gc KO phenotype provides a protective effect on the graft due to decreased human antibody recognition and graft injury.
Type of Medium:
Online Resource
ISSN:
0908-665X
,
1399-3089
DOI:
10.1111/xen.2018.25.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2011995-1
