Development of a 3D In Vitro Model of Dupuytren's Disease as a Platform for Drug Screening

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064211%3A_____%2F26%3AW0000048" target="_blank" >RIV/00064211:_____/26:W0000048 - isvavai.cz</a>

Výsledek na webu

<a href="https://oadoi.org/10.1007/s12195-026-00885-2" target="_blank" >https://oadoi.org/10.1007/s12195-026-00885-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12195-026-00885-2" target="_blank" >10.1007/s12195-026-00885-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Development of a 3D In Vitro Model of Dupuytren's Disease as a Platform for Drug Screening

Popis výsledku v původním jazyce

BackgroundDupuytren's disease (DD) is a common fibrotic disorder of the hand, characterized by progressive thickening and contracture of the palmar and digital fascia. Surgical excision remains the primary treatment; however, there are currently no therapies to prevent disease progression or recurrence. This study aims to develop a 3D in vitro model to test novel antifibrotic therapies. The model is based on decellularized pathological DD tissue seeded with patient-derived fibroblasts, capturing the role of both cellular and extracellular matrix components in disease progression.MethodsFibrotic DD tissues were obtained from surgical excisions, sectioned, and decellularized. In parallel, primary fibroblasts were isolated from patient samples. The decellularized extracellular matrices (dECMs) were characterized with respect to biochemical composition, collagen structure, and mechanical properties. Fibroblasts were seeded onto the dECMs and cultured stepwise to initially promote proliferation, followed by differentiation into myofibroblasts. Secretomes of cells cultivated on the established 3D model were compared to those from conventional 2D cultivations. To evaluate the models relevance and effectiveness we tested the antifibrotic drug minoxidil.ResultsThe dECMs retained the pathological architecture and mechanical properties of native DD tissue, although individual ECM components were reduced after decellularization. Fibroblasts successfully adhered, proliferated, and repopulated the scaffold. The relevance of the 3D model was demonstrated by the presence of myofibroblasts with disease-relevant secretome. The responsiveness to the drug minoxidil was significantly more complex in the 3D model than in conventional 2D cultures.ConclusionWe demonstrated that dECM seeded with DD fibroblasts represents a relevant 3D in vitro model of Dupuytren's disease. The model enables antifibrotic drug screening, as demonstrated by the testing of minoxidil. Our model provides a reproducible platform also suitable for the investigation of cells and ECM contributions to palmar fascial fibrosis.

Název v anglickém jazyce

Development of a 3D In Vitro Model of Dupuytren's Disease as a Platform for Drug Screening

Popis výsledku anglicky

BackgroundDupuytren's disease (DD) is a common fibrotic disorder of the hand, characterized by progressive thickening and contracture of the palmar and digital fascia. Surgical excision remains the primary treatment; however, there are currently no therapies to prevent disease progression or recurrence. This study aims to develop a 3D in vitro model to test novel antifibrotic therapies. The model is based on decellularized pathological DD tissue seeded with patient-derived fibroblasts, capturing the role of both cellular and extracellular matrix components in disease progression.MethodsFibrotic DD tissues were obtained from surgical excisions, sectioned, and decellularized. In parallel, primary fibroblasts were isolated from patient samples. The decellularized extracellular matrices (dECMs) were characterized with respect to biochemical composition, collagen structure, and mechanical properties. Fibroblasts were seeded onto the dECMs and cultured stepwise to initially promote proliferation, followed by differentiation into myofibroblasts. Secretomes of cells cultivated on the established 3D model were compared to those from conventional 2D cultivations. To evaluate the models relevance and effectiveness we tested the antifibrotic drug minoxidil.ResultsThe dECMs retained the pathological architecture and mechanical properties of native DD tissue, although individual ECM components were reduced after decellularization. Fibroblasts successfully adhered, proliferated, and repopulated the scaffold. The relevance of the 3D model was demonstrated by the presence of myofibroblasts with disease-relevant secretome. The responsiveness to the drug minoxidil was significantly more complex in the 3D model than in conventional 2D cultures.ConclusionWe demonstrated that dECM seeded with DD fibroblasts represents a relevant 3D in vitro model of Dupuytren's disease. The model enables antifibrotic drug screening, as demonstrated by the testing of minoxidil. Our model provides a reproducible platform also suitable for the investigation of cells and ECM contributions to palmar fascial fibrosis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)

Projekt

<a href="/cs/project/NU22-10-00072" target="_blank" >NU22-10-00072: Vytvoření 3D modelu clubfoot a Dupuytrenovy choroby a následné testování antifibrotických látek</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2026

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

CELLULAR AND MOLECULAR BIOENGINEERING

ISSN

1865-5025

e-ISSN

1865-5033

Svazek periodika

19

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

111-127

Kód UT WoS článku

001664310100001

EID výsledku v databázi Scopus

—