Regulation of Epithelial-to-Mesenchymal Transition Using Biomimetic Fibrous Scaffolds.

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Epithelial-to-mesenchymal transition (EMT) is crucial in development and disease.
• The role of matrix topography in EMT is not fully understood.
• Basement membrane microstructure may influence EMT dynamics.

Purpose of the Study:

• To investigate the impact of synthetic matrix fiber diameter on EMT.
• To determine if matrix microstructure influences cell response to EMT inducers.
• To elucidate the role of basement membrane topography in epithelial cell behavior.

Main Methods:

• Fabrication of poly(ε-caprolactone) (PCL) scaffolds with varying fiber diameters (0.5 μm and 5 μm) using electrospinning.
• Conjugation of cell-adhesive peptides to scaffold surfaces.
• Culture of Madin-Darby Canine Kidney (MDCK) cells on scaffolds and induction of EMT using hepatocyte growth factor (HGF).
• Analysis of cell morphology, adhesion, and marker expression.

Main Results:

• MDCK cells exhibited distinct phenotypes based on scaffold fiber diameter.
• Cells on 0.5 μm scaffolds showed epithelial characteristics, while cells on 5 μm scaffolds appeared more fibroblastic.
• HGF induced significant EMT, including scattering and mesenchymal marker upregulation, on 0.5 μm scaffolds but not on 5 μm scaffolds.
• Fiber diameter significantly modulated the cellular response to EMT induction.

Conclusions:

• Matrix fiber diameter is a critical factor regulating EMT.
• Scaffold microstructure can control epithelial cell plasticity and response to external stimuli.
• Altering basement membrane fiber diameter may influence disease progression by affecting epithelial organization.