Abstract
Renal fibrosis is a hallmark of progressive renal diseases. To date, there is a lack of effective therapeutics for the treatment of renal fibrosis, in part due to the scarcity of clinically relevant translational disease models. Since the early 1920s, hand-cut tissue slices have been used as a means to better understand organ (patho)physiology in a variety of scientific fields. From that time, the equipment and methodology for the preparation of tissue slices has continuously improved, thereby expanding the applicability of the model. Nowadays, precision-cut kidney slices (PCKS) have been demonstrated to be an extremely valuable translation model for renal (patho)physiology, bridging the gap between preclinical and clinical research. A key feature of PCKS is that the slices contain all cell types and acellular components of the whole organ in the original configuration while preserving cell-cell and cell-matrix interactions. In this chapter, we describe how to prepare PCKS and how the model can be implemented in fibrosis research.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Mehal WZ, Iredale J, Friedman SL (2011) Scraping fibrosis: expressway to the core of fibrosis. Nat Med 175(17):552–553. https://doi.org/10.1038/nm0511-552
Bigaeva E, Puerta Cavanzo N, Stribos EGD et al (2020) Predictive value of precision-cut kidney slices as an ex vivo screening platform for therapeutics in human renal fibrosis. Pharmaceutics 12:459. https://doi.org/10.3390/pharmaceutics12050459
Jensen CG, Jensen MS, Tingskov SJ et al (2021) Local inhibition of Indoleamine 2,3-dioxygenase mitigates renal fibrosis. Biomedicines 9:856 9:856. https://doi.org/10.3390/BIOMEDICINES9080856
Jensen MS, Mutsaers HAM, Tingskov SJ et al (2019) Activation of the prostaglandin E2 EP2 receptor attenuates renal fibrosis in unilateral ureteral obstructed mice and human kidney slices. Acta Physiol 227. https://doi.org/10.1111/apha.13291
Stribos EGD, Luangmonkong T, Leliveld AM et al (2016) Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis. Transl Res 170:8–16e1. https://doi.org/10.1016/j.trsl.2015.11.007
Poosti F, Pham BT, Oosterhuis D et al (2015) Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo. Dis Model Mech 8:1227–1236. https://doi.org/10.1242/dmm.020172
De Kanter R, Olinga P, De Jager MH et al (1999) Organ slices as an in vitro test system for drug metabolism in human liver, lung and kidney. Toxicol Vitr 13:737–744. https://doi.org/10.1016/S0887-2333(99)00047-8
Bartucci R, van der Meer AZ, Boersma YL et al (2021) Nanoparticle-induced inflammation and fibrosis in ex vivo murine precision-cut liver slices and effects of nanoparticle exposure conditions. Arch Toxicol 95:1267–1285. https://doi.org/10.1007/S00204-021-02992-7
Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburgs contributions to current concepts of cancer metabolism. Nat Publ Gr 11:325–337. https://doi.org/10.1038/nrc3038
Warburg O, Minami S (1923) Versuche an Überlebendem Carcinom-gewebe. Klin Wochenschr 2:776–777. https://doi.org/10.1007/BF01712130
Krumdieck C (1980) A new instrument for the rapid preparation of tissue slices. Anal Biochem 104:123
Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–148
Ahmann FR, Garewal HS, Schifman RON et al (1987) Intracellular adenosine triphosphate as a measure of human tumor cell viability and drug modulated growth. Vitr Cell Dev Biol 23:474–480
Luciano RL, Moeckel GW (2019) Update on the native kidney biopsy: core curriculum 2019. Am J Kidney Dis 73:404–415. https://doi.org/10.1053/J.AJKD.2018.10.011
Street JM, Souza ACP, Alvarez-Prats A et al (2014) Automated quantification of renal fibrosis with Sirius Red and polarization contrast microscopy. Physiol Rep 2:e12088. https://doi.org/10.14814/PHY2.12088
De Kanter R, De Jager MH, Draaisma AL et al (2002) Drug-metabolizing activity of human and rat liver, lung, kidney and intestine slices. https://doi.org/10.1080/00498250110112006
Walker PD, Cavallo T, Bonsib SM (2004) Practice guidelines for the renal biopsy. Mod Pathol 1712(17):1555–1563. https://doi.org/10.1038/modpathol.3800239
Acknowledgments
This work was supported by grants from the Karen Elise Jensen Foundation, the Novo Nordisk Foundation (NNF19OC0054481) and Lundbeckfonden (R368-2021-726).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Jensen, M.S., Merrild, C., Nørregaard, R., Olinga, P., Mutsaers, H.A.M. (2023). Standardized Protocol for the Preparation of Precision-Cut Kidney Slices: A Translational Model of Renal Fibrosis. In: Hewitson, T.D., Toussaint, N.D., Smith, E.R. (eds) Kidney Research. Methods in Molecular Biology, vol 2664. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3179-9_9
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3179-9_9
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3178-2
Online ISBN: 978-1-0716-3179-9
eBook Packages: Springer Protocols