Modulation of designer biomimetic matrices for optimized differentiated intestinal epithelial cultures

Wang Xi (1) , Jad Saleh (1) , Ayako Yamada (2) , Caterina Tomba (3) , Barbara Mercier (1) , Sébastien Janel (4) , Tien Dang (1) , Matis Soleilhac (1) , Aurélie Djemat (5) , Huiqiong Wu (1) , Béatrice Romagnolo (6) , Frank Lafont (4) , René-Marc Mège (1) , Yong Chen (2) , Delphine Delacour (1)

1 IJM (UMR_7592) - Institut Jacques Monod
2 PASTEUR - Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640)
3 INL - Institut des Nanotechnologies de Lyon
4 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
5 Animal Core Facility Buffon
6 DRC - [Institut Cochin] Département Développement, Reproduction et Cancer

The field of intestinal biology is thirstily searching for different culture methods that complement the limitations of organoids, particularly the lack of a differentiated intestinal compartment. While being recognized as an important milestone for basic and translational biological studies, many primary cultures of intestinal epithelium (IE) rely on empirical trials using hydrogels of various stiffness, whose mechanical impact on epithelial organization remains vague until now. Here, we report the development of hydrogel scaffolds with a range of elasticities and their influence on IE expansion, organization, and differentiation. On stiff substrates (>5 kPa), mouse IE cells adopt a flat cell shape and detach in the short-term. In contrast, on soft substrates (80-500 Pa), they sustain for a long-term, pack into high density, develop columnar shape with improved apical-basal polarity and differentiation marker expression, a phenotype reminiscent of features in vivo mouse IE. We then developed a soft gel molding process to produce 3D Matrigel scaffolds of close-to-nature stiffness, which support and maintain a culture of mouse IE into crypt-villus architecture. Thus, the present work is up-to-date informative for the design of biomaterials for ex vivo intestinal models, offering self-renewal in vitro culture that emulates the mouse IE.

Domaines: Sciences du Vivant [q-bio]

Wang Xi, Jad Saleh, Ayako Yamada, Caterina Tomba, Barbara Mercier, et al.. Modulation of designer biomimetic matrices for optimized differentiated intestinal epithelial cultures. Biomaterials, 2022, 282, pp.121380. ⟨10.1016/j.biomaterials.2022.121380⟩. ⟨hal-03598543⟩