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Updated: Mar 11, 2026

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
Published on: February 15, 2019
Human corneal fibroblast migration and extracellular matrix synthesis during stromal repair: Role played by
Patricia Gallego-Muñoz1, Lucía Ibares-Frías1,2, José A Garrote3
1Departamento de Biología Celular, Histología y Farmacología. Facultad de Medicina. Grupo de Investigación Reconocido: Técnicas Ópticas para el Diagnóstico, Universidad de Valladolid, Valladolid, Spain.
Abstract:
The development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, a mechanical wound model was developed to study the influence of the GFs basic fibroblast GF (bFGF), platelet-derived GF (PDGF-BB) and transforming GF-β1 (TGFβ1) on ECM protein production and cellular migration. Our results show that mechanical wounding provokes the autocrine release of bFGF and TGFβ1 at different time points during the wound closure. The HCF response to PDGF-BB was a rapid closure due to fast cellular migration associated with a high focal adhesion replacement and a high expression of collagen and proteoglycans, producing nonfibrotic healing. bFGF stimulated nonfibrotic ECM production and limited the migration process. Finally, TGFβ1 induced expression of the fibrotic markers collagen type III and α5β1 integrin, and it inhibited cellular migration due to the formation of focal adhesions with a low turnover rate. The novel in vitro HCF mechanical wound model can be used to understand the role played by GFs in human corneal repair. The model can also be used to test the effects of different treatments aimed at improving the healing process. Copyright © 2016 John Wiley & Sons, Ltd.
Insights
Platelet-derived growth factor (PDGF-BB) promotes non-fibrotic corneal healing by enhancing cell migration and extracellular matrix production. Transforming growth factor-beta1 (TGFβ1) induces fibrosis by increasing collagen III and inhibiting cell migration.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Tissue Engineering
Background:
- Corneal transparency restoration after injury is crucial.
- Fibrosis during corneal wound healing impairs vision.
- Growth factors (GFs) influence extracellular matrix (ECM) production and cell migration in corneal fibroblasts.
Purpose of the Study:
- To investigate the effects of basic fibroblast GF (bFGF), platelet-derived GF (PDGF-BB), and transforming GF-β1 (TGFβ1) on human corneal fibroblast (HCF) ECM protein expression and cellular migration in an in vitro mechanical wound model.
- To understand the role of GFs in human corneal repair and identify potential therapeutic targets for non-fibrotic healing.
Main Methods:
- Development of an in vitro mechanical wound model using human corneal fibroblasts (HCFs).
- Treatment of HCFs with bFGF, PDGF-BB, and TGFβ1.
- Analysis of ECM protein expression (collagen types I and III, perlecan), cell migration, and focal adhesion dynamics.
Main Results:
- Mechanical wounding induced autocrine release of bFGF and TGFβ1.
- PDGF-BB promoted rapid wound closure via enhanced cell migration and non-fibrotic ECM production.
- bFGF stimulated non-fibrotic ECM production while limiting migration.
- TGFβ1 induced fibrotic markers (collagen type III, α5β1 integrin) and inhibited cell migration by forming stable focal adhesions.
Conclusions:
- The in vitro HCF mechanical wound model effectively simulates corneal repair processes.
- PDGF-BB shows potential for promoting non-fibrotic corneal healing.
- TGFβ1 is identified as a key mediator of corneal fibrosis.
- This model can be utilized to evaluate treatments for improving corneal wound healing and preventing fibrosis.
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