0599455 - FGÚ 2025 RIV US eng J - Článek v odborném periodiku
Doubková, Martina - Knitlová, Jarmila - Vondrášek, David - Eckhardt, Adam - Novotný, T. - Ošťádal, M. - Filová, Elena - Bačáková, Lucie
Harnessing the Biomimetic Effect of Macromolecular Crowding in the Cell-Derived Model of Clubfoot Fibrosis.
Biomacromolecules. Roč. 25, č. 10 (2024), s. 6485-6502. ISSN 1525-7797. E-ISSN 1526-4602
Grant CEP: GA MZd(CZ) NU22-10-00072; GA MŠMT(CZ) EH22_008/0004562; GA MŠMT(CZ) EF18_046/0016045
Grant ostatní: AV ČR(CZ) AP2202
Program: Akademická prémie - Praemium Academiae
Výzkumná infrastruktura: Czech-BioImaging III - 90250
Institucionální podpora: RVO:67985823
Klíčová slova: clubfoot * fibrosis * cell culture * biopolymers
Obor OECD: Orthopaedics
Impakt faktor: 5.5, rok: 2023 ; AIS: 1.018, rok: 2023
Způsob publikování: Open access
Web výsledku:
https://doi.org/10.1021/acs.biomac.4c00653DOI: https://doi.org/10.1021/acs.biomac.4c00653

Fibrotic changes in pediatric clubfoot provide an opportunity to improve corrective therapy and prevent relapses with targeted drugs. This study defines the parameters of clubfoot fibrosis and presents a unique analysis of a simple pseudo-3D in vitro model for disease-specific high-throughput drug screening experiments. The model combines clubfoot-derived fibroblasts with a biomimetic cultivation environment induced by the water-soluble polymers Ficoll and Polyvinylpyrrolidone, utilizing the principle of macromolecular crowding. We achieved higher conversion of soluble collagen into insoluble collagen, accelerated formation of the extracellular matrix layer and upregulated fibrosis-related genes in the mixed Ficoll environment. To test the model, we evaluated the effect of a potential antifibrotic drug, minoxidil, emphasizing collagen content and cross-linking. While the model amplified overall collagen deposition, minoxidil effectively blocked the expression of lysyl hydroxylases, which are responsible for the increased occurrence of specific collagen cross-linking in various fibrotic tissues. This limited the formation of collagen cross-link in both the model and control environments. Our findings provide a tool for expanding preclinical research for clubfoot and similar fibroproliferative conditions.
Trvalý link: https://hdl.handle.net/11104/0356881