Journal article
Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood
AK Bongoni, E Salvaris, S Nordling, N Klymiuk, E Wolf, DL Ayares, R Rieben, PU Magnusson, PJ Cowan
Scientific Reports | NATURE PORTFOLIO | Published : 2017
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..
View full abstractGrants
Awarded by Swiss National Science Foundation (SNSF)
Awarded by Research Endowment Fund of St Vincent's Hospital Melbourne
Awarded by National Health & Medical Research Council of Australia (NHMRC) - European Union (EU) Collaborative Research program
Awarded by Swiss National Science Foundation (SNF)
Awarded by National Health and Medical Research Council of Australia
Funding Acknowledgements
These studies were supported by the Swiss National Science Foundation (SNSF) (Fellowship: P2BEP3_155459), the Research Endowment Fund of St Vincent's Hospital Melbourne (REF# 70189), and the National Health & Medical Research Council of Australia (NHMRC) - European Union (EU) Collaborative Research program (project #1074171). The authors thank Annegret Wuensch, Andrea Baehr from the Institute of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilian University, Munich, Germany for providing aortic endothelial cells from genetically modified pigs. The authors also thank staff at the Immunology Research Centre (IRC), St. Vincent's Hospital Melbourne, Australia, for technical support and advice.