Chronic kidney disease is a major health concern, and experimental models bridging
the gap between animal studies and clinical research are currently lacking. Here,
we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease.
PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and
cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie,
uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined
to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene
expressions were characterized. Finally, to validate the model, renal fibrogenesis
was induced using transforming growth factor β1 (TGF-β1). Preparation of PCKSs induced
an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis
as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin
1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced
by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular
diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger
RNA levels suggesting that our model might not be suitable to study the role of podocytes
in renal pathology. Moreover, TGF-β1 exposure augmented fibrosis, as illustrated by
an increased expression of multiple fibrosis markers including COL1A1, FN1, and α-smooth
muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and
appear to be a promising model to investigate renal diseases, for example, renal fibrosis.
Moreover, the human origin of PCKSs makes this model very suitable for translational
research.
Abbreviations:
ATP (adenosine triphosphate), BCRP (breast cancer resistance protein), CKD (chronic kidney disease), COL1A1 (collagen type 1A1), ECM (extracellular matrix), ESRD (end-stage renal disease), FN1 (fibronectin 1), GAPDH (glyceraldehyde 3-phosphate dehydrogenase), 7-HCG (7-hydroxycoumarin glucuronide), HPLC (high-performance liquid chromatography), HSP47 (heat shock protein 47), LDH (lactate dehydrogenase), OAT (organic anion transporter), OATP4C1 (organic anion transporting polypeptide 4C1), PAI (plasminogen activator inhibitor), PAS (Periodic acid–Schiff), PCKSs (precision-cut kidney slices), PDGFB (platelet-derived growth factor subunit B), qPCR (quantitative real-time polymerase chain reaction), TGF-β1 (transforming growth factor β1), UGT (Uridine 5'-diphospho-glucuronosyltransferase), α-SMA (α-smooth muscle actin)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 25, 2015
Accepted:
November 20,
2015
Received in revised form:
November 18,
2015
Received:
July 23,
2015
Footnotes
Peter Olinga and Henricus A.M. Mutsaers contributed equally to this work.
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
