Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood

Abstract Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with a glycocalyx-like layer and may inhibit (xeno)transplant-associated activation of the plasma cascade systems. Here, we investigated the use of CHC to protect WT and genetically modified (...

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Autores principales:	Anjan K. Bongoni, Evelyn Salvaris, Sofia Nordling, Nikolai Klymiuk, Eckhard Wolf, David L. Ayares, Robert Rieben, Peetra U. Magnusson, Peter J. Cowan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/644500d90d4649d2a075e77455a6fe32
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spelling	oai:doaj.org-article:644500d90d4649d2a075e77455a6fe322021-12-02T12:32:28ZSurface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood10.1038/s41598-017-04898-w2045-2322https://doaj.org/article/644500d90d4649d2a075e77455a6fe322017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04898-whttps://doaj.org/toc/2045-2322Abstract Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with a glycocalyx-like layer and may inhibit (xeno)transplant-associated activation of the plasma cascade systems. Here, we investigated the use of CHC to protect WT and genetically modified (GTKO.hCD46.hTBM) pig aortic endothelial cells (PAEC) in two pig-to-human in vitro xenotransplantation settings. Model 1: incubation of untreated or hTNFα-treated PAEC with 10% human plasma induced complement C3b/c and C5b-9 deposition, cellular activation and coagulation activation in WT and GTKO.hCD46.hTBM PAEC. Coating of untreated or hTNFα-treated PAEC with CHC (100 µg/ml) protected against human plasma-induced endothelial activation and damage. Model 2: PAEC were grown on microcarrier beads, coated with CHC, and incubated with non-anticoagulated whole human blood. Genetically modified PAEC significantly prolonged clotting time of human blood (115.0 ± 16.1 min, p < 0.001) compared to WT PAEC (34.0 ± 8.2 min). Surface CHC significantly improved the human blood compatibility of PAEC, as shown by increased clotting time (WT: 84.3 ± 11.3 min, p < 0.001; GTKO.hCD46.hTBM: 146.2 ± 20.4 min, p < 0.05) and reduced platelet adhesion, complement activation, coagulation activation and inhibition of fibrinolysis. The combination of CHC coating and genetic modification provided the greatest compatibility with human blood, suggesting that pre-transplant perfusion of genetically modified porcine organs with CHC may benefit post-transplant xenograft function.Anjan K. BongoniEvelyn SalvarisSofia NordlingNikolai KlymiukEckhard WolfDavid L. AyaresRobert RiebenPeetra U. MagnussonPeter J. CowanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anjan K. Bongoni Evelyn Salvaris Sofia Nordling Nikolai Klymiuk Eckhard Wolf David L. Ayares Robert Rieben Peetra U. Magnusson Peter J. Cowan Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
description	Abstract Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with a glycocalyx-like layer and may inhibit (xeno)transplant-associated activation of the plasma cascade systems. Here, we investigated the use of CHC to protect WT and genetically modified (GTKO.hCD46.hTBM) pig aortic endothelial cells (PAEC) in two pig-to-human in vitro xenotransplantation settings. Model 1: incubation of untreated or hTNFα-treated PAEC with 10% human plasma induced complement C3b/c and C5b-9 deposition, cellular activation and coagulation activation in WT and GTKO.hCD46.hTBM PAEC. Coating of untreated or hTNFα-treated PAEC with CHC (100 µg/ml) protected against human plasma-induced endothelial activation and damage. Model 2: PAEC were grown on microcarrier beads, coated with CHC, and incubated with non-anticoagulated whole human blood. Genetically modified PAEC significantly prolonged clotting time of human blood (115.0 ± 16.1 min, p < 0.001) compared to WT PAEC (34.0 ± 8.2 min). Surface CHC significantly improved the human blood compatibility of PAEC, as shown by increased clotting time (WT: 84.3 ± 11.3 min, p < 0.001; GTKO.hCD46.hTBM: 146.2 ± 20.4 min, p < 0.05) and reduced platelet adhesion, complement activation, coagulation activation and inhibition of fibrinolysis. The combination of CHC coating and genetic modification provided the greatest compatibility with human blood, suggesting that pre-transplant perfusion of genetically modified porcine organs with CHC may benefit post-transplant xenograft function.
format	article
author	Anjan K. Bongoni Evelyn Salvaris Sofia Nordling Nikolai Klymiuk Eckhard Wolf David L. Ayares Robert Rieben Peetra U. Magnusson Peter J. Cowan
author_facet	Anjan K. Bongoni Evelyn Salvaris Sofia Nordling Nikolai Klymiuk Eckhard Wolf David L. Ayares Robert Rieben Peetra U. Magnusson Peter J. Cowan
author_sort	Anjan K. Bongoni
title	Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
title_short	Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
title_full	Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
title_fullStr	Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
title_full_unstemmed	Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
title_sort	surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/644500d90d4649d2a075e77455a6fe32
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Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood

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