A Synovium-on-Chip Platform to Study Multicellular Interactions in Arthritis.

Area of Science:

• Biomedical Engineering
• Immunology
• Rheumatology

Background:

• Arthritis progression involves complex cellular interactions within the synovium.
• Understanding this crosstalk is limited by the lack of human-relevant preclinical models.
• The synovium's role in modulating arthritis requires further investigation.

Purpose of the Study:

• To develop a novel, compartmentalized synovium-on-chip (SoC) platform.
• To investigate cellular crosstalk between fibroblast-like synoviocytes (FLS), macrophages, and endothelial cells.
• To model synovial inflammation and study arthritis mechanisms in vitro.

Main Methods:

• Co-culture of primary human FLS, THP-1-derived macrophages, and endothelial cells on a microporous membrane.
• Utilizing a microscale architecture to sustain cell viability and markers for over ten days.
• Employing machine-learning-based image analysis to assess cellular interactions and phenotypic shifts.

Main Results:

• The SoC platform successfully maintained co-cultures and lineage-specific markers.
• FLS migration through the membrane induced endothelial lumen remodeling.
• TNF-α stimulation established synovial inflammation with significant cytokine upregulation.
• Demonstrated dynamic, migration-driven interactions between synovium and vasculature.

Conclusions:

• The developed SoC platform is a powerful tool for studying arthritis progression.
• It facilitates the investigation of intercellular communication in the synovium.
• Provides a novel in vitro model for identifying therapeutic targets for arthritis.