Advanced Cellular Models for Drug Testing and Discovery to Target Cardiac Fibrosis Progression
4 affiliations
- 1Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy
- 2IRCCS Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, Italy
- 3IRCCS Neuromed, 86077 Pozzilli, Italy
- 4Institute of Biochemistry and Cell Biology, National Council of Research (IBBC-CNR), 00015 Monterotondo, Italy
Abstract
Cardiac fibrosis is a complex and dynamic pathological process, central for cardiac repair, characterised by continuous cell–cell and cell–matrix interactions. Three-dimensional (3D) models are gaining increasing relevance, compared with traditional two-dimensional (2D) cellular setups, due to their ability to recapitulate key features of the fibrotic microenvironment at different levels of complexity, including cellular heterogeneity, spatial organisation and tissue mechanical properties. These systems have enabled a deeper investigation of fibrosis mechanobiology and the mechanosensitive pathways involved in disease progression, contributing to the identification of potential therapeutic targets for cardiac repair. Increasing biological complexity can reveal therapeutic responses that remain undetected in conventional models; however, the predictive value of 3D systems has so far been confirmed in vivo only for a limited number of platforms and compounds. The role of 3D models is therefore expanding beyond disease modelling towards platforms for the screening and evaluation of antifibrotic strategies, pointing to increasingly functional cardiac reparative strategies. Here, we distinguish model complexity, biological fidelity and demonstrated predictive value, compare current platforms according to their validation level and limitations, and discuss the benchmarks and standards required for their routine use in antifibrotic drug discovery. From this perspective, the development of systems that are not necessarily more sophisticated, but progressively more informative and predictive, may help bridge the gap between conventional 2D in vitro models and animal studies, ultimately improving the translational relevance of preclinical evaluation.
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BibTeX
@article{icolaro2026advanced,
title = {{Advanced Cellular Models for Drug Testing and Discovery to Target Cardiac Fibrosis Progression}},
author = {Francesca Icolaro and Isotta Chimenti and Claudia Cozzolino and Antonella Bordin and Virginia Pontecorvi and Giacomo Frati and Elena De Falco and Erica Floris and Vittorio Picchio and Francesca Pagano},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219729},
url = {https://www.mdpi.com/1422-0067/27/21/9729},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Advanced Cellular Models for Drug Testing and Discovery to Target Cardiac Fibrosis Progression
AU - Francesca Icolaro
AU - Isotta Chimenti
AU - Claudia Cozzolino
AU - Antonella Bordin
AU - Virginia Pontecorvi
AU - Giacomo Frati
AU - Elena De Falco
AU - Erica Floris
AU - Vittorio Picchio
AU - Francesca Pagano
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219729
UR - https://www.mdpi.com/1422-0067/27/21/9729
AB - Cardiac fibrosis is a complex and dynamic pathological process, central for cardiac repair, characterised by continuous cell–cell and cell–matrix interactions. Three-dimensional (3D) models are gaining increasing relevance, compared with traditional two-dimensional (2D) cellular setups, due to their ability to recapitulate key features of the fibrotic microenvironment at different levels of complexity, including cellular heterogeneity, spatial organisation and tissue mechanical properties. These systems have enabled a deeper investigation of fibrosis mechanobiology and the mechanosensitive pathways involved in disease progression, contributing to the identification of potential therapeutic targets for cardiac repair. Increasing biological complexity can reveal therapeutic responses that remain undetected in conventional models; however, the predictive value of 3D systems has so far been confirmed in vivo only for a limited number of platforms and compounds. The role of 3D models is therefore expanding beyond disease modelling towards platforms for the screening and evaluation of antifibrotic strategies, pointing to increasingly functional cardiac reparative strategies. Here, we distinguish model complexity, biological fidelity and demonstrated predictive value, compare current platforms according to their validation level and limitations, and discuss the benchmarks and standards required for their routine use in antifibrotic drug discovery. From this perspective, the development of systems that are not necessarily more sophisticated, but progressively more informative and predictive, may help bridge the gap between conventional 2D in vitro models and animal studies, ultimately improving the translational relevance of preclinical evaluation.
SN - 1422-0067
ER -