title: Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.
abstract: Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-β1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-β1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-β1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Bao Tung
authors.initials: BT
authors.lastname: Pham
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Wouter Tobias
authors.initials: WT
authors.lastname: van Haaften
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Dorenda
authors.initials: D
authors.lastname: Oosterhuis
authors.affiliation: Pathology Friesland Foundation, Leeuwarden, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Nieken
authors.affiliation: Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Inge Anne Maria
authors.initials: IA
authors.lastname: de Graaf
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands P.Olinga@rug.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: Olinga
keywords: Ex vivo model; intestinal fibrosis; precision‐cut intestinal slice