Abstract

A Three-Dimensional Model of the Neurovascular Unit Using Human Ex Vivo Brain Tissue

Brian O'Grady, Post Doc, Vanderbilt

The neurovascular unit (NVU) is a multicellular, complex structure that facilitates molecular transport of required nutrients and excludes potentially harmful components from entering brain tissue. Recent novel methods and newly developed stem cell differentiation strategies have improved in vitro modeling of the NVU[1]. However, these models are often oversimplified and do not fully recapitulate the complex multi-cellular hierarchy and cellular interactions that are required to create a physiologically relevant NVU model[2]. To address this limitation, Dr. O’Grady recently developed a new biomaterial functionalized with a peptide from the extracellular epitope of N-Cadherin that promotes maturation of single-cell suspensions of iPSC-derived glutamatergic neurons into synaptically connected networks. In addition, he found that this hydrogel supports robust and continuous growth of primary human ex vivo arterial- and capillary-specific brain vasculature. The newly formed vasculature consisted of the correct anatomical hierarchy for capillaries and arteries similar to what is seen in vivo. He embedded the ex vivo human brain tissue in microfluidic devices generated from high-resolution 3D printed molds, and induced anastomosis to form a lumen-perfusable NVU-on-a-chip. Dr. O’Grady believes this technology will provide an exceptional opportunity for investigating new therapeutic options in vitro that could ultimately impact clinical care for neurological diseases.