Novel high throughput 3D ECM remodeling assay identifies MEK as key driver of fibrotic fibroblast activity.

ABSTRACT: In fibrotic tissues, activated fibroblasts remodel the collagen-rich extracellular matrix (ECM). Intervening with this process represents a candidate therapeutic strategy to attenuate disease progression. Models that generate quantitative data on 3D fibroblast-mediated ECM remodeling with the reproducibility and throughput needed for drug testing are lacking. Here, we develop a model that fits this purpose and produces combined quantitative information on drug efficacy and cytotoxicity. We use microinjection robotics to design patterns of fibrillar collagen-embedded fibroblast clusters and apply automated microscopy and image analysis to quantify ECM remodeling between-, and cell viability within clusters of TGFβ-activated primary human skin or lung fibroblasts. We apply this assay to comp

SUBMITTER: Liao CY 

PROVIDER: S-EPMC12059351 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature