Programmable Living Units for Emulating Pancreatic Tumor-Stroma Interplay.
Fiche publication
Date publication
avril 2022
Journal
Advanced healthcare materials
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MANO João F.
Tous les auteurs :
Monteiro MV, Rocha M, Gaspar VM, Mano JF
Lien Pubmed
Résumé
Bioengineering close-to-native in vitro models that emulate tumors bioarchitecture and microenvironment is highly appreciable for improving disease modelling toolboxes. Herein, pancreatic cancer living units - so termed cancer-on-a-bead models - were generated. Such user-programmable in vitro platforms exhibit biomimetic multi-compartmentalization and tunable integration of cancer associated stromal elements. These stratified units can be rapidly assembled in-air, exhibit reproducible morphological features, tunable size, and recapitulate spatially resolved tumor-stroma ECM niches. Compartmentalization of pancreatic cancer and stromal cells in well-defined ECM microenvironments stimulated the secretion of key biomolecular effectors including TGF-β and IL-1β, closely emulating the signatures of human pancreatic tumors. Cancer-on-a-bead models also display increased drug resistance to chemotherapeutics when compared to their reductionistic counterparts, reinforcing the importance to differentially model ECM components inclusion and their spatial stratification as observed in vivo. Beyond providing a universal technology that enables spatial modularity in tumor-stroma elements bioengineering, this study provides a scalable, in-air fabrication of ECM-tunable 3D platforms that can be leveraged for recapitulating differential matrix composition occurring in other human neoplasia's. This article is protected by copyright. All rights reserved.
Mots clés
3D in vitro tumor models, pancreatic tumor microenvironment, preclinical drug screening, superhydrophobic surfaces
Référence
Adv Healthc Mater. 2022 Apr 14;:e2102574