TY - JOUR
T1 - Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation
T2 - Preclinical investigations in pig and mouse
AU - Nordling, Sofia
AU - Brännström, Johan
AU - Carlsson, Fredrik
AU - Lu, Bo
AU - Salvaris, Evelyn
AU - Wanders, Alkwin
AU - Buijs, Jos
AU - Estrada, Sergio
AU - Tolmachev, Vladimir
AU - Cowan, Peter J.
AU - Lorant, Tomas
AU - Magnusson, Peetra U.
N1 - Funding Information:
The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement n°602699 (DIREKT), NHMRC/EU grant #1074171, the Uppsala BIO’s BIO-X program, the Swedish Governmental Agency for Innovation Systems (Vinnova), the Kidney Foundation, the Lars-Erik Gelin Memorial Foundation and the Bergholm Foundation. Imaging was performed with equipment maintained by the Science for Life Lab BioVis Platform Uppsala University, and histology images were provided by the Science for Life Lab Tissue Profiling Facility Uppsala University.
Publisher Copyright:
© 2018 The Author(s).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.
AB - Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.
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U2 - 10.1038/s41598-018-21463-1
DO - 10.1038/s41598-018-21463-1
M3 - Article
C2 - 29581529
AN - SCOPUS:85044529085
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 5220
ER -