Publicaciones científicas
- [SISTEMAS MICROFISIOLÓGICOS Y BIOLOGÍA CUANTITATIVA]
- [INGENIERÍA BIOMÉDICA]
- [INNOVACIÓN TECNOLÓGICA]
Tumor Organoids Grown in Mixed-Composition Hydrogels Recapitulate the Plasticity of Pancreatic Cancers
Ioritz Sorzabal-Bellido 1, Xabier Morales 2, Iván Cortés-Domínguez 1 2 3 4, Maider Esparza 2, Lucía Grande 2, Pedro Castillo 1, Silvia Larumbe 5, María Monteserín 5, Shruthi Narayanan 6, Mariano Ponz-Sarvise 4 6 7, Silve Vicent 4 6 8 9, Carlos Ortiz-de-Solórzano 1 2 8 10
Abstract
Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit pronounced phenotypic plasticity, alternating between a treatment-sensitive classical phenotype and a more aggressive basal-like state associated with drug resistance and poor prognosis. The frequent coexistence of these phenotypes complicates patient stratification and the selection of effective therapies. Tumor-derived organoids are valuable tools for drug screening; however, their clinical relevance relies on how accurately they recapitulate the phenotypic and functional characteristics of the original tumors. In this study, we present a quantitative analysis of how hydrogel composition influences the phenotype, tissue remodeling, metabolism, and drug resistance of PDAC organoids. Organoids were cultured within three types of hydrogels: Matrigel, collagen-I, and a mixture of collagen-I and Matrigel. Our results demonstrate that: (i) PDAC organoids grown in Matrigel exhibit a classical phenotype, with metabolic and drug response profiles similar to those of low-physiological two-dimensional cultures; (ii) Organoids grown in collagen-containing hydrogels, particularly those in collagen-Matrigel composites, faithfully recapitulate basal-like tumors, characterized by epithelial-to-mesenchymal transition, tissue remodeling, metabolic activity, and drug resistance; (iii) TGFβ induces an exacerbated, highly invasive basal-like phenotype. Summarizing, our findings highlight the importance of 3D hydrogel composition in modulating PDAC organoid phenotype and behavior and suggest collagen-Matrigel hydrogels as the most suitable matrix for modeling PDAC biology.
CITA DEL ARTÍCULO Gels. 2025 Jul 21;11(7):562. doi: 10.3390/gels11070562.

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