Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Emilia Bigaeva, University of Groningen
  • ,
  • Nataly Puerta Cavanzo, University of Groningen
  • ,
  • Elisabeth G.D. Stribos, University of Groningen
  • ,
  • Amos J. de Jong, University of Groningen
  • ,
  • Carin Biel, University of Groningen
  • ,
  • Henricus A.M. Mutsaers
  • Michael S. Jensen
  • Rikke Nørregaard
  • Anna M. Leliveld, University of Groningen
  • ,
  • Igle J. de Jong, University of Groningen
  • ,
  • Jan Luuk Hillebrands, University of Groningen
  • ,
  • Harry van Goor, University of Groningen
  • ,
  • Miriam Boersema, University of Groningen
  • ,
  • Ruud A. Bank, University of Groningen
  • ,
  • Peter Olinga, University of Groningen

Animal models are a valuable tool in preclinical research. However, limited predictivity of human biological responses in the conventional models has stimulated the search for reliable preclinical tools that show translational robustness. Here, we used precision-cut kidney slices (PCKS) as a model of renal fibrosis and investigated its predictive capacity for screening the effects of anti-fibrotics. Murine and human PCKS were exposed to TGFβ or PDGF pathway inhibitors with established anti-fibrotic efficacy. For each treatment modality, we evaluated whether it affected: (1) culture-induced collagen type I gene expression and interstitial accumulation; (2) expression of markers of TGFβ and PDGF signaling; and (3) expression of inflammatory markers. We summarized the outcomes of published in vivo animal and human studies testing the three inhibitors in renal fibrosis, and drew a parallel to the PCKS data. We showed that the responses of murine PCKS to anti-fibrotics highly corresponded with the known in vivo responses observed in various animal models of renal fibrosis. Moreover, our results suggested that human PCKS can be used to predict drug efficacy in clinical trials. In conclusion, our study demonstrated that the PCKS model is a powerful predictive tool for ex vivo screening of putative drugs for renal fibrosis.

OriginalsprogEngelsk
Artikelnummer459
TidsskriftPharmaceutics
Vol/bind12
Nummer5
Antal sider31
ISSN1999-4923
DOI
StatusUdgivet - maj 2020

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