Authors
L Leonie van Leeuwen, Mitchel JR Ruigrok, Benedikt M Kessler, Henri GD Leuvenink, Peter Olinga
Publication date
2024/2
Journal
British Journal of Pharmacology
Volume
181
Issue
3
Pages
464-479
Description
Background and Purpose
Fibrosis in kidney allografts is a major post‐transplant complication that contributes to graft failure. Lately, multiple potent inhibitors of fibrosis‐related pathways have been developed such as galunisertib, an inhibitor of the transforming growth factor‐beta (TGF‐β/TGFβ1) signalling pathway. This drug, however, poses risks for adverse effects when administered systemically. Therefore, we devised a new repurposing strategy in which galunisertib is administered ex vivo. We combined machine perfusion and tissue slices to explore the antifibrotic effects of galunisertib in renal grafts.
Experimental Approach
Porcine kidneys were subjected to 30 min of warm ischaemia, 24 h of oxygenated hypothermic machine perfusion and 6 h of normothermic machine perfusion with various treatments (i.e. untreated control, TGFβ1, galunisertib or TGFβ1 + galunisertib; n = 8 kidneys per group). To …
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