Modeling Biochemical Gradients In Vitro to Control Cell Compartmentalization in a Microengineered 3D Model of the Intestinal Epithelium.

Autor: Altay G; Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 15-21, Barcelona, 08028, Spain.; Institut de l'Audition, Institut Pasteur, INSERM, Université de Paris, Paris, 75012, France., Abad-Lázaro A; Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 15-21, Barcelona, 08028, Spain., Gualda EJ; SLN Research Facility, Institute of Photonic Sciences (ICFO), Mediterranean Technology Park, Av. Carl Friedrich Gauss 3 Castelldefels, Barcelona, 08860, Spain., Folch J; Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 15-21, Barcelona, 08028, Spain., Insa C; Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 15-21, Barcelona, 08028, Spain., Tosi S; Advanced Digital Microscopy Core Facility (ADMCF), Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, Barcelona, 08028, Spain., Hernando-Momblona X; Colorectal Cancer Laboratory, Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, Barcelona, 08028, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, 08028, Spain., Batlle E; Colorectal Cancer Laboratory, Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, Barcelona, 08028, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, 08028, Spain.; ICREA, Passeig Lluís Companys 23, Barcelona, 08010, Spain., Loza-Álvarez P; SLN Research Facility, Institute of Photonic Sciences (ICFO), Mediterranean Technology Park, Av. Carl Friedrich Gauss 3 Castelldefels, Barcelona, 08860, Spain., Fernández-Majada V; Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 15-21, Barcelona, 08028, Spain., Martinez E; Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 15-21, Barcelona, 08028, Spain.; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Av. Monforte de Lemos 3-5 Pabellón 11 Planta 0, Madrid, 28029, Spain.; Department of Electronics and Biomedical Engineering, University of Barcelona (UB), Martí i Franquès 1, Barcelona, 08028, Spain.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2022 Nov; Vol. 11 (22), pp. e2201172. Date of Electronic Publication: 2022 Sep 15.
DOI: 10.1002/adhm.202201172
Abstrakt: Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how are they sensed by the epithelium is still not fully understood. Here a new in vitro model of the small intestine based on primary epithelial cells (i), apically accessible (ii), with native tissue mechanical properties and controlled mesh size (iii), 3D villus-like architecture (iv), and precisely controlled biomolecular gradients of the ISC niche (v) is presented. Biochemical gradients are formed through hydrogel-based scaffolds by free diffusion from a source to a sink chamber. To confirm the establishment of spatiotemporally controlled gradients, light-sheet fluorescence microscopy and in-silico modeling are employed. The ISC niche biochemical gradients coming from the stroma and applied along the villus axis lead to the in vivo-like compartmentalization of the proliferative and differentiated cells, while changing the composition and concentration of the biochemical factors affects the cellular organization along the villus axis. This novel 3D in vitro intestinal model derived from organoids recapitulates both the villus-like architecture and the gradients of ISC biochemical factors, thus opening the possibility to study in vitro the nature of such gradients and the resulting cellular response.
(© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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