Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.

Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to f...

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Autores principales:	Pascal Hoffmann, Nadine Schnepel, Marion Langeheine, Katrin Künnemann, Guntram A Grassl, Ralph Brehm, Bettina Seeger, Gemma Mazzuoli-Weber, Gerhard Breves
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/acc3a08ea5c045fd84f4c15937a3baae
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spelling	oai:doaj.org-article:acc3a08ea5c045fd84f4c15937a3baae2021-12-02T20:17:40ZIntestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.1932-620310.1371/journal.pone.0256143https://doaj.org/article/acc3a08ea5c045fd84f4c15937a3baae2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256143https://doaj.org/toc/1932-6203Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to farm animals. The 3R principles of Russel and Burch were achieved using intestinal organoids of porcine jejunum. These organoids seem to be a promising tool to generate species-specific in vitro models of intestinal epithelium. 3D Organoids were grown in an extracellular matrix and characterized by qPCR. Organoids were also seeded on permeable filter supports in order to generate 2D epithelial monolayers. The organoid-based 2D monolayers were characterized morphologically and were investigated regarding their potential to study physiological transport properties and pathophysiological processes. They showed a monolayer structure containing different cell types. Moreover, their functional activity was demonstrated by their increasing transepithelial electrical resistance over 18 days and by an active glucose transport and chloride secretion. Furthermore, the organoid-based 2D monolayers were also confronted with cholera toxin derived from Vibrio cholerae as a proof of concept. Incubation with cholera toxin led to an increase of short-circuit current indicating an enhanced epithelial chloride secretion, which is a typical characteristic of cholera infections. Taken this together, our model allows the investigation of physiological and pathophysiological mechanisms focusing on the small intestine of pigs. This is in line with the 3R principle and allows the reduction of classical animal experiments.Pascal HoffmannNadine SchnepelMarion LangeheineKatrin KünnemannGuntram A GrasslRalph BrehmBettina SeegerGemma Mazzuoli-WeberGerhard BrevesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256143 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pascal Hoffmann Nadine Schnepel Marion Langeheine Katrin Künnemann Guntram A Grassl Ralph Brehm Bettina Seeger Gemma Mazzuoli-Weber Gerhard Breves Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.
description	Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to farm animals. The 3R principles of Russel and Burch were achieved using intestinal organoids of porcine jejunum. These organoids seem to be a promising tool to generate species-specific in vitro models of intestinal epithelium. 3D Organoids were grown in an extracellular matrix and characterized by qPCR. Organoids were also seeded on permeable filter supports in order to generate 2D epithelial monolayers. The organoid-based 2D monolayers were characterized morphologically and were investigated regarding their potential to study physiological transport properties and pathophysiological processes. They showed a monolayer structure containing different cell types. Moreover, their functional activity was demonstrated by their increasing transepithelial electrical resistance over 18 days and by an active glucose transport and chloride secretion. Furthermore, the organoid-based 2D monolayers were also confronted with cholera toxin derived from Vibrio cholerae as a proof of concept. Incubation with cholera toxin led to an increase of short-circuit current indicating an enhanced epithelial chloride secretion, which is a typical characteristic of cholera infections. Taken this together, our model allows the investigation of physiological and pathophysiological mechanisms focusing on the small intestine of pigs. This is in line with the 3R principle and allows the reduction of classical animal experiments.
format	article
author	Pascal Hoffmann Nadine Schnepel Marion Langeheine Katrin Künnemann Guntram A Grassl Ralph Brehm Bettina Seeger Gemma Mazzuoli-Weber Gerhard Breves
author_facet	Pascal Hoffmann Nadine Schnepel Marion Langeheine Katrin Künnemann Guntram A Grassl Ralph Brehm Bettina Seeger Gemma Mazzuoli-Weber Gerhard Breves
author_sort	Pascal Hoffmann
title	Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.
title_short	Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.
title_full	Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.
title_fullStr	Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.
title_full_unstemmed	Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.
title_sort	intestinal organoid-based 2d monolayers mimic physiological and pathophysiological properties of the pig intestine.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/acc3a08ea5c045fd84f4c15937a3baae
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Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.

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