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Immunocompetent Alveolus-on-Chip Model for Studying Alveolar Mucosal Immune Responses

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Alveolocapillary model system to study alveolar re-epithelialization.

Coen H M P Willems¹, Luc J I Zimmermann, Patricia J L T Sanders

¹Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, The Netherlands.

Experimental Cell Research

|October 2, 2012

Summary

The pulmonary microvascular endothelium slows lung tissue repair. Close cell-to-cell connections between endothelial and alveolar cells mediate this effect, impacting re-epithelialization.

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Area of Science:

Pulmonary research
Cell biology
Tissue engineering

Background:

The pulmonary alveolocapillary barrier is crucial for lung function.
Understanding cell interactions is key to lung tissue repair.

Purpose of the Study:

To investigate the microvascular endothelium's role in lung tissue re-epithelialization.
To establish an in vitro model of the pulmonary alveolocapillary barrier.

Main Methods:

Developed an in vitro bilayer model using human microvascular endothelial cells (HPMECs) and alveolar type II-like cells (A549).
Utilized fluorescent proteins (EGFP and mCherry) for real-time monitoring of cell layer integrity and wound healing.
Employed transmission electron microscopy and immunohistochemistry to analyze cell-cell contacts and junction formation.

Main Results:

Human microvascular endothelial cells (HPMECs) significantly slowed re-epithelialization in proximity to A549 cells.
Electron microscopy revealed cell protrusions through the membrane and close heterocellular contacts.
Immunohistochemistry confirmed the presence of gap, tight, and adherens junctions between HPMECs and A549 cells.
Functional gap-junctional communication was observed between the cell types, inhibitable by connexin mimetic peptides.

Conclusions:

The pulmonary microvascular endothelium influences the rate of lung tissue re-epithelialization.
Heterocellular junctions and communication between endothelial and alveolar cells play a role in this process.