A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells

Ben M. Maoz, Anna Herland, Edward A. Fitzgerald, Thomas Grevesse, Charles Vidoudez, Alan R. Pacheco, Sean P. Sheehy, Tae Eun Park, Stephanie Dauth, Robert Mannix, Nikita Budnik, Kevin Shores, Alexander Cho, Janna C. Nawroth, Daniel Segrè, Bogdan Budnik, Donald E. Ingber, Kevin Kit Parker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood–brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.

Original languageEnglish
Pages (from-to)865-877
Number of pages13
JournalNature Biotechnology
Volume36
Issue number9
DOIs
StatePublished - 1 Oct 2018

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