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

Autor: Gizem Altay, Aina Abad-Lázaro, Emilio J. Gualda, Jordi Folch, Claudia Insa, Sébastien Tosi, Xavier Hernando-Momblona, Eduard Batlle, Pablo Loza-Álvarez, Vanesa Fernández-Majada, Elena Martinez
Přispěvatelé: Universitat Politècnica de Catalunya. Departament d'Enginyeria Agroalimentària i Biotecnologia, Universitat Politècnica de Catalunya. HorPTA - Horticultura: producció, transformació i aprofitament
Rok vydání: 2022
Předmět:
Zdroj: Advanced Healthcare Materials. 11:2201172
ISSN: 2192-2659
2192-2640
DOI: 10.1002/adhm.202201172
Popis: 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. he authors thank Rene Fabregas for the advice on the in-silico model. The authors also thank Jordi Comelles, María García and Enara Larrañaga for the fruitful discussions. Funding for this project was provided by European Union's Horizon 2020 ERC grant agreements No 647863 (COMIET) and No 884623 (residualCRC), the CERCA Programme/Generalitat de Catalunya (2017-SGR-1079 and 2017-SGR-698), Laserlab-Europe EU-H2020 grant agreement No 871124, the Spanish Ministry of Economy and Competitiveness (Severo Ochoa Program for Centers of Excellence in R&D 2016–2019 and CEX2019-000910-S), the Spanish Ministry of Science (PID2020-119917RB-I00) and also by the Fundació Privada Cellex and the Fundació Mir-Puig. The authors thank Barcelona Institute of Science and Technology (BIST) for the funding of ENGUT project through Ignite Programme. The authors gratefully acknowledge the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) for the funding of G.A. through FI-DGR 2014 and to MINECO/FEDER Ramón y Cajal program (RYC-2015-17935) for the funding of E.G. The results presented here reflect only the views of the authors; the European Commission is not responsible for any use that may be made of the information it contains.
Databáze: OpenAIRE
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