Brain Microenvironment Models

A major thrust in the group is the development of in vitro models that recapitulate various aspects of the neuromuscular unit.  We have started with a model of the blood-brain barrier composed of primary human endothelial cells derived from iPSCs as well as primary human pericytes and/or astrocytes.  We have established barriers in both transwells and microfluidc devices, characterized by high transendothelial electrical resistance (>2000 ohm cm^2) and low solute permeability coefficients (<10^-6 cm/s).   We have used the models to investigate the impact of flow-induced shear stress on receptor-mediated transport of nanoparticles across the BBB as well as cytokine-mediated permeabilization of the BBB.  We are also using the platform as the basis for a model of the neuromuscular unit, which will be used to investigate the biological consequences of persistent microglia activation on the BBB and neurons.