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

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Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis. / Bigaeva, Emilia; Cavanzo, Nataly Puerta; Stribos, Elisabeth G.D.; de Jong, Amos J.; Biel, Carin; Mutsaers, Henricus A.M.; Jensen, Michael S.; Nørregaard, Rikke; Leliveld, Anna M.; de Jong, Igle J.; Hillebrands, Jan Luuk; van Goor, Harry; Boersema, Miriam; Bank, Ruud A.; Olinga, Peter.

I: Pharmaceutics, Bind 12, Nr. 5, 459, 05.2020.

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

Harvard

Bigaeva, E, Cavanzo, NP, Stribos, EGD, de Jong, AJ, Biel, C, Mutsaers, HAM, Jensen, MS, Nørregaard, R, Leliveld, AM, de Jong, IJ, Hillebrands, JL, van Goor, H, Boersema, M, Bank, RA & Olinga, P 2020, 'Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis', Pharmaceutics, bind 12, nr. 5, 459. https://doi.org/10.3390/pharmaceutics12050459

APA

Bigaeva, E., Cavanzo, N. P., Stribos, E. G. D., de Jong, A. J., Biel, C., Mutsaers, H. A. M., Jensen, M. S., Nørregaard, R., Leliveld, A. M., de Jong, I. J., Hillebrands, J. L., van Goor, H., Boersema, M., Bank, R. A., & Olinga, P. (2020). Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis. Pharmaceutics, 12(5), [459]. https://doi.org/10.3390/pharmaceutics12050459

CBE

Bigaeva E, Cavanzo NP, Stribos EGD, de Jong AJ, Biel C, Mutsaers HAM, Jensen MS, Nørregaard R, Leliveld AM, de Jong IJ, Hillebrands JL, van Goor H, Boersema M, Bank RA, Olinga P. 2020. Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis. Pharmaceutics. 12(5):Article 459. https://doi.org/10.3390/pharmaceutics12050459

MLA

Vancouver

Author

Bigaeva, Emilia ; Cavanzo, Nataly Puerta ; Stribos, Elisabeth G.D. ; de Jong, Amos J. ; Biel, Carin ; Mutsaers, Henricus A.M. ; Jensen, Michael S. ; Nørregaard, Rikke ; Leliveld, Anna M. ; de Jong, Igle J. ; Hillebrands, Jan Luuk ; van Goor, Harry ; Boersema, Miriam ; Bank, Ruud A. ; Olinga, Peter. / Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis. I: Pharmaceutics. 2020 ; Bind 12, Nr. 5.

Bibtex

@article{2c05bc59bd2d4880b55b8bee93a4b356,
title = "Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis",
abstract = "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.",
keywords = "Antifibrotic drugs, Galunisertib, Imatinib, Pirfenidone, Precision-cut kidney slices, Renal fibrosis",
author = "Emilia Bigaeva and Cavanzo, {Nataly Puerta} and Stribos, {Elisabeth G.D.} and {de Jong}, {Amos J.} and Carin Biel and Mutsaers, {Henricus A.M.} and Jensen, {Michael S.} and Rikke N{\o}rregaard and Leliveld, {Anna M.} and {de Jong}, {Igle J.} and Hillebrands, {Jan Luuk} and {van Goor}, Harry and Miriam Boersema and Bank, {Ruud A.} and Peter Olinga",
year = "2020",
month = may,
doi = "10.3390/pharmaceutics12050459",
language = "English",
volume = "12",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "5",

}

RIS

TY - JOUR

T1 - Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis

AU - Bigaeva, Emilia

AU - Cavanzo, Nataly Puerta

AU - Stribos, Elisabeth G.D.

AU - de Jong, Amos J.

AU - Biel, Carin

AU - Mutsaers, Henricus A.M.

AU - Jensen, Michael S.

AU - Nørregaard, Rikke

AU - Leliveld, Anna M.

AU - de Jong, Igle J.

AU - Hillebrands, Jan Luuk

AU - van Goor, Harry

AU - Boersema, Miriam

AU - Bank, Ruud A.

AU - Olinga, Peter

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - Antifibrotic drugs

KW - Galunisertib

KW - Imatinib

KW - Pirfenidone

KW - Precision-cut kidney slices

KW - Renal fibrosis

UR - http://www.scopus.com/inward/record.url?scp=85084997321&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics12050459

DO - 10.3390/pharmaceutics12050459

M3 - Journal article

C2 - 32443499

AN - SCOPUS:85084997321

VL - 12

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 5

M1 - 459

ER -