While in vivo models are the gold standard for addressing blood-brain barrier (BBB) functionality and drug safety, they suffer from the lack of human complementarity, with an estimated 80 percent of candidate drugs successfully tested in small animals failing in human clinical trials. While such failures are not solely attributable to a lack of adequate BBB models, there is a large need for more relevant models.
To meet this need, Navy research chemists have constructed synthetic human blood vessels using human brain-derived endothelial cells and incorporated these into a tissue model that contains astrocytes and other neurons and microglia. Multi-cell type microvessels, in this case, synthetic Human Endothelial Microvessels (HEMVs), which incorporate cells such as astrocytes and pericytes yield a highly representative BBB in vitro model with a functional lumen containing brain-derived microvascular endothelial cells and a polymer wall containing human astrocytes and pericytes.
Construction of this model leverages a microfluidic method based on sheath flow to generate hollow microvessels that can incorporate common BBB cells. This results in a superior model which eliminates the need for unreliable transwell membrane-based assays. The synthetic blood vessels include a hollow tube having a lumen and a polymer wall comprising extracellular matrix components, the tube has an outer diameter of 50 to 250 μm with living brain microvascular endothelial cells within the lumen and living astrocytes disposed within the polymer wall.
Applications for these microvessels include BBB permeability studies, drug delivery research, and brain-targeted diseases resulting from viral or bacterial infection.
- Incorporates multiple cell types into the microvessel
- Brain capillary-like microvessels are more representative in size to observed capillaries in vivo and are capable of being positioned into any in vitro model
- Microvessels are hollow by design and the ability to perfuse material through these cell-laden structures vastly improves their utility, a process that is simply not possible using the transwell approach
- This model supports endothelial sprouting beyond the fabricated microvessel, allowing full tissue integration and better tissue maintenance than is currently provided by other rigid microchannel devices
- US application number 20180064527 available for license
- Potential for collaboration with Navy researchers