Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis

Area of Science:

• Biomedical Engineering
• Cell Biology
• Pulmonary Medicine

Background:

• Lung fibrosis is a progressive scarring disease with no cure, involving myofibroblast accumulation and vascular remodeling.
• The interaction between myofibroblasts and vasculature in lung fibrosis is not well understood, with conflicting data on angiogenesis and vessel density.

Purpose of the Study:

• To develop a microphysiological system to model lung fibrosis and investigate myofibroblast-vascular crosstalk.
• To determine the role of lung myofibroblasts in vascular changes during fibrosis.

Main Methods:

• A microfluidic device was used to culture lung myofibroblasts and endothelial cells in a 3D system mimicking lung fibrosis.
• Analysis of endothelial cell behavior, including sprouting, morphology, and permeability, was performed.
• Cytokine levels (TGF-β1, VEGF) and the effects of pharmacological interventions were assessed.

Main Results:

• Lung myofibroblasts in the 3D system exhibited anti-angiogenic and anti-vasculogenic properties.
• Decreased endothelial sprouting, altered vascular morphology, and increased vascular permeability were observed.
• These vascular changes were linked to increased TGF-β1 and reduced VEGF secretion by myofibroblasts.

Conclusions:

• The developed microphysiological system effectively models lung fibrosis and myofibroblast-vascular interactions.
• Lung myofibroblasts actively inhibit angiogenesis and vascularization, mediated by specific cytokine signaling.
• This model shows promise for screening anti-fibrotic therapies targeting vascular dysfunction.