Integration of immune cells in organs-on-chips: a tutorial

Area of Science:

• Immunology
• Biomedical Engineering
• Infectious Diseases

Background:

• Viral and bacterial infections present global health challenges requiring novel therapeutic strategies.
• Understanding the human immune system's response during infection is crucial for developing new treatments.
• Existing organs-on-chip (OOC) models require enhanced immune components to fully replicate complex physiological processes.

Purpose of the Study:

• To provide a practical guide for constructing an organs-on-chip (OOC) model simulating acute infection.
• To investigate the recruitment of circulating immune cells into infected tissues using an OOC system.
• To detail the modeling of the immune cell extravasation cascade within an engineered microenvironment.

Main Methods:

• Description of the multi-step extravasation cascade in vivo.
• Guidance on designing OOC devices for modeling immune cell migration.
• Incorporation of endothelial, epithelial, and immune cells within a hydrogel extracellular matrix (ECM).
• Creation of chemotactic gradients to direct immune cell movement.

Main Results:

• The review outlines the essential components for an OOC model of acute infection.
• It details methods for replicating immune cell migration from blood into tissue.
• Focus is placed on the hydrogel ECM's role in simulating the interstitial space for immune cell migration.

Conclusions:

• This tutorial review offers a practical framework for developing advanced OOC models.
• The developed models can investigate immune cell migration dynamics during infection.
• These OOC systems represent a significant advancement in modeling complex immune responses to pathogens.