Počet záznamů: 1
Harnessing the Biomimetic Effect of Macromolecular Crowding in the Cell-Derived Model of Clubfoot Fibrosis
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SYSNO ASEP 0599455 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Harnessing the Biomimetic Effect of Macromolecular Crowding in the Cell-Derived Model of Clubfoot Fibrosis Tvůrce(i) Doubková, Martina (FGU-C) ORCID, RID
Knitlová, Jarmila (FGU-C) RID, ORCID
Vondrášek, David (FGU-C) ORCID, SAI
Eckhardt, Adam (FGU-C) RID, ORCID
Novotný, T. (CZ)
Ošťádal, M. (CZ)
Filová, Elena (FGU-C) RID, ORCID
Bačáková, Lucie (FGU-C) RID, ORCIDZdroj.dok. Biomacromolecules. - : American Chemical Society - ISSN 1525-7797
Roč. 25, č. 10 (2024), s. 6485-6502Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova clubfoot ; fibrosis ; cell culture ; biopolymers Obor OECD Orthopaedics CEP NU22-10-00072 GA MZd - Ministerstvo zdravotnictví EH22_008/0004562 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF18_046/0016045 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura Czech-BioImaging III - 90250 - Ústav molekulární genetiky AV ČR, v. v. i. Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 001302826500001 EID SCOPUS 85202902215 DOI https://doi.org/10.1021/acs.biomac.4c00653 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2025 Elektronická adresa https://doi.org/10.1021/acs.biomac.4c00653
Počet záznamů: 1