Renal fibrosis is one of the main pathophysiological processes underlying the progression of chronic kidney disease and kidney allograft failure. The objective of this study was to establish a drug screening platform for renal fibrosis based on human precision-cut kidney slices (PCKS).
PCKS were prepared from functional and macroscopically healthy renal tissue obtained from 16 patients following tumor nephrectomies. The slices were treated for 48 h with human transforming growth factor-β1 (TGF-β) in the absence or presence of various drugs. Using Western blotting and gene expression arrays, it was shown that TGF-β induced fibrosis in human PCKS. In addition, the tested putative anti-fibrotic compounds altered TGF-β-induced pro-fibrotic gene expression in human PCKS, and it was found that the individual compounds modulate fairly distinct sets of genes.
In conclusion, this study revealed that PCKS are a feasible system to test drug efficacy and elucidate mechanisms of action.
An animal-free preclinical drug screening platform based on human precision-cut kidney slices
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