Permeability across a novel microfluidic blood-tumor barrier model

Area of Science:

• Biomedical Engineering
• Neuroscience
• Pharmacology

Background:

• Developing effective treatments for central nervous system (CNS) tumors is hindered by the lack of translatable in vitro blood-tumor barrier (BTB) models.
• Understanding vascular alterations at the blood-brain barrier (BBB) in the presence of tumors is crucial for advancing CNS cancer therapies.

Purpose of the Study:

• To characterize a novel microfluidic model of the BTB, serving as a reference to a standard BBB model.
• To incorporate physiological factors like flow and shear stress into an in vitro BTB model.

Main Methods:

• A microfluidic device was engineered with distinct compartments for endothelial cells and either astrocytes (BBB model) or cancer cells (BTB model).
• Cells communicated across a porous interface, and the model incorporated physiological flow and shear stress.
• Permeability of passive markers and efflux transporter function (P-gp) were assessed and compared between the BTB and BBB models.

Main Results:

• The BTB model exhibited significantly higher permeability for Sulforhodamine 101 compared to the BBB model.
• Increased permeability was observed in the BTB model for molecules across a range of sizes (600 Da to 60 kDa).
• The efflux transporter P-gp demonstrated intact function in both models, with permeability rates consistent with in vivo data.

Conclusions:

• The developed microfluidic BTB model is a novel, commercially available tool for studying brain tumors.
• This dynamic in vitro model accurately replicates in vivo permeability and efflux characteristics.
• The model provides a valuable platform for CNS drug development and understanding BTB pathophysiology.