Publication

Predictive Value of Precision-Cut Kidney Slices as an Ex Vivo Screening Platform for Therapeutics in Human Renal Fibrosis

Bigaeva, E., Puerta Cavanzo, N., 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., 18-May-2020, In : Pharmaceutics. 12, 5, 31 p., 459.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Bigaeva, E., Puerta Cavanzo, N., Stribos, E. G. D., de Jong, A. J., Biel, C., Mutsaers, H. A. M., ... 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

Author

Bigaeva, Emilia ; Puerta Cavanzo, Nataly ; 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. In: Pharmaceutics. 2020 ; Vol. 12, No. 5.

Harvard

Bigaeva, E, Puerta Cavanzo, N, Stribos, EGD, de Jong, AJ, Biel, C, Mutsaers, HAM, Jensen, MS, Nørregaard, R, Leliveld, AM, de Jong, IJ, Hillebrands, J-L, 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, vol. 12, no. 5, 459. https://doi.org/10.3390/pharmaceutics12050459

Standard

Predictive Value of Precision-Cut Kidney Slices as an Ex Vivo Screening Platform for Therapeutics in Human Renal Fibrosis. / Bigaeva, Emilia; Puerta Cavanzo, Nataly; 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.

In: Pharmaceutics, Vol. 12, No. 5, 459, 18.05.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Bigaeva E, Puerta Cavanzo N, Stribos EGD, de Jong AJ, Biel C, Mutsaers HAM et al. Predictive Value of Precision-Cut Kidney Slices as an Ex Vivo Screening Platform for Therapeutics in Human Renal Fibrosis. Pharmaceutics. 2020 May 18;12(5). 459. https://doi.org/10.3390/pharmaceutics12050459


BibTeX

@article{4de479cd5e724808896ad4c8c7987bc3,
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 TGF beta 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 TGF beta 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 = "renal fibrosis, precision-cut kidney slices, antifibrotic drugs, pirfenidone, galunisertib, imatinib, GROWTH-FACTOR RECEPTOR, TGF-BETA, IMATINIB MESYLATE, PIRFENIDONE PREVENTS, GENE-EXPRESSION, PROGRESSION, MECHANISMS, MODEL, LIVER, PDGF",
author = "Emilia Bigaeva and {Puerta Cavanzo}, Nataly 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 Jan-Luuk Hillebrands and {van Goor}, Harry and Miriam Boersema and Bank, {Ruud A} and Peter Olinga",
year = "2020",
month = "5",
day = "18",
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 - Puerta Cavanzo, Nataly

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 - 2020/5/18

Y1 - 2020/5/18

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 TGF beta 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 TGF beta 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 TGF beta 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 TGF beta 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 - renal fibrosis

KW - precision-cut kidney slices

KW - antifibrotic drugs

KW - pirfenidone

KW - galunisertib

KW - imatinib

KW - GROWTH-FACTOR RECEPTOR

KW - TGF-BETA

KW - IMATINIB MESYLATE

KW - PIRFENIDONE PREVENTS

KW - GENE-EXPRESSION

KW - PROGRESSION

KW - MECHANISMS

KW - MODEL

KW - LIVER

KW - PDGF

U2 - 10.3390/pharmaceutics12050459

DO - 10.3390/pharmaceutics12050459

M3 - Article

VL - 12

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 5

M1 - 459

ER -

ID: 125712416