@misc{9238718,
  abstract     = {{Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease driven by persistent fibroblast activation, abnormal epithelial to mesenchymal signaling and excessive extracellular matrix (ECM) remodeling. Better pre-clinical models are needed to reproduce these processes and to support antifibrotic drug development. This thesis tested whether an in vitro co-culture model can generate ECM biomarker readouts that reflect IPF-like interstitial remodeling and basement membrane (BM) turnover. 

A modified Scar-in-a-Jar approach was established using primary normal human lung fibroblasts and human bronchial epithelial cells (Beas-2b). Fibrotic remodeling was induced with transforming growth factor beta (TGF-β) and fibrotic cocktail (FC). Supernatants were collected over time and analyzed by competitive ELISAs for biomarkers of collagen formation (type I, III, IV, VI), fibronectin remodeling and collagen IV degradation. Dose-dependent effects of the anti-fibrotic drugs Nintedanib and Bexotegrast were evaluated in the co-culture setup.
Profibrotic stimulation consistently increased biomarkers linked to interstitial ECM formation, with the strongest responses in 2,000 fibroblasts + 20,000 epithelial cells co-culture, that we selected since in this ratio we could see the additive effect of the epithelial cells in the fibroblast culture. In contrast, collagen IV BM biomarkers showed limited dynamics, suggesting that BM fragment generation and release were not robust under these conditions. In this co-culture setup, Nintedanib reduced fibroblast-associated collagen formation signals, while Bexotegrast produced variable responses. 

Overall, the model supports fibroblast-driven interstitial remodeling relevant to IPF and indicated refinements needed to better capture BM turnover and epithelial damage biology.}},
  author       = {{Klokova, Xeniya}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{PROFILING EXTRACELLULAR MATRIX REMODELING IN AN IN VITRO FIBROBLAST AND EPITHELIAL CELL CO-CULTURE MODEL}},
  year         = {{2026}},
}