Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function

Abstract Intestinal organoids have emerged as a powerful in vitro tool for studying intestinal biology due to their resemblance to in vivo tissue at the structural and functional levels. However, their sphere-like geometry prevents access to the apical side of the epithelium, making them unsuitable...

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Autores principales:	Gizem Altay, Enara Larrañaga, Sébastien Tosi, Francisco M. Barriga, Eduard Batlle, Vanesa Fernández-Majada, Elena Martínez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eefe1a4a21a2472280147542e31a1d4d
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spelling	oai:doaj.org-article:eefe1a4a21a2472280147542e31a1d4d2021-12-02T15:08:10ZSelf-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function10.1038/s41598-019-46497-x2045-2322https://doaj.org/article/eefe1a4a21a2472280147542e31a1d4d2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46497-xhttps://doaj.org/toc/2045-2322Abstract Intestinal organoids have emerged as a powerful in vitro tool for studying intestinal biology due to their resemblance to in vivo tissue at the structural and functional levels. However, their sphere-like geometry prevents access to the apical side of the epithelium, making them unsuitable for standard functional assays designed for flat cell monolayers. Here, we describe a simple method for the formation of epithelial monolayers that recapitulates the in vivo-like cell type composition and organization and that is suitable for functional tissue barrier assays. In our approach, epithelial monolayer spreading is driven by the substrate stiffness, while tissue barrier function is achieved by the basolateral delivery of medium enriched with stem cell niche and myofibroblast-derived factors. These monolayers contain major intestinal epithelial cell types organized into proliferating crypt-like domains and differentiated villus-like regions, closely resembling the in vivo cell distribution. As a unique characteristic, these epithelial monolayers form functional epithelial barriers with an accessible apical surface and physiologically relevant transepithelial electrical resistance values. Our technology offers an up-to-date and novel culture method for intestinal epithelium, providing an in vivo-like cell composition and distribution in a tissue culture format compatible with high-throughput drug absorption or microbe-epithelium interaction studies.Gizem AltayEnara LarrañagaSébastien TosiFrancisco M. BarrigaEduard BatlleVanesa Fernández-MajadaElena MartínezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gizem Altay Enara Larrañaga Sébastien Tosi Francisco M. Barriga Eduard Batlle Vanesa Fernández-Majada Elena Martínez Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
description	Abstract Intestinal organoids have emerged as a powerful in vitro tool for studying intestinal biology due to their resemblance to in vivo tissue at the structural and functional levels. However, their sphere-like geometry prevents access to the apical side of the epithelium, making them unsuitable for standard functional assays designed for flat cell monolayers. Here, we describe a simple method for the formation of epithelial monolayers that recapitulates the in vivo-like cell type composition and organization and that is suitable for functional tissue barrier assays. In our approach, epithelial monolayer spreading is driven by the substrate stiffness, while tissue barrier function is achieved by the basolateral delivery of medium enriched with stem cell niche and myofibroblast-derived factors. These monolayers contain major intestinal epithelial cell types organized into proliferating crypt-like domains and differentiated villus-like regions, closely resembling the in vivo cell distribution. As a unique characteristic, these epithelial monolayers form functional epithelial barriers with an accessible apical surface and physiologically relevant transepithelial electrical resistance values. Our technology offers an up-to-date and novel culture method for intestinal epithelium, providing an in vivo-like cell composition and distribution in a tissue culture format compatible with high-throughput drug absorption or microbe-epithelium interaction studies.
format	article
author	Gizem Altay Enara Larrañaga Sébastien Tosi Francisco M. Barriga Eduard Batlle Vanesa Fernández-Majada Elena Martínez
author_facet	Gizem Altay Enara Larrañaga Sébastien Tosi Francisco M. Barriga Eduard Batlle Vanesa Fernández-Majada Elena Martínez
author_sort	Gizem Altay
title	Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
title_short	Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
title_full	Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
title_fullStr	Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
title_full_unstemmed	Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
title_sort	self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/eefe1a4a21a2472280147542e31a1d4d
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Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function

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