A Cost-Effective and Easy to Assemble 3D Human Microchannel Blood-Brain Barrier Model and Its Application in Tumor Cell Adhesion Under Flow.

Abstract

By utilizing polydimethylsiloxane (PDMS), collagen hydrogel, and a cell line for human cerebral microvascular endothelial cells, we produced a 3D microchannel blood-brain barrier (BBB) model under physiological flow. This 3D BBB has a circular-shaped cross-section and a diameter of ~100 μm, which can properly mimic the cerebral microvessel responsible for material exchange between the circulating blood and brain tissue. The permeability of the 3D microchannel BBB to a small molecule (sodium fluorescein with a molecular weight of 376) and that to a large molecule (Dex-70k) are the same as those of rat cerebral microvessels. This 3D BBB model can replicate the effects of a plasma protein, orosomucoid, a cytokine, vascular endothelial growth factor (VEGF), and an enzyme, heparinase III, on either rat cerebral or mesenteric microvessesels in terms of permeability and the modulation of glycocalyx (heparan sulfate). It can also replicate the adhesion of a breast cancer cell, MDA-MB-231, in rat mesenteric microvessels under no treatment or treatments with VEGF, orosomucoid, and heparinase III. Because of difficulties in accessing human cerebral microvessels, this inexpensive and easy to assemble 3D human BBB model can be applied to investigate BBB-modulating mechanisms in health and in disease and to develop therapeutic interventions targeting tumor metastasis to the brain.