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A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells
Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Tel Aviv Univ, Dept Biomed Engn, Fac Engn, Tel Aviv, Israel.;Tel Aviv Univ, Sagol Sch Neurosci, Tel Aviv, Israel.;Tel Aviv Univ, Ctr Nanosci & Nanotechnol, Tel Aviv, Israel..
KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems. Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Karolinska Inst, Dept Neurosci, Swedish Med Nanosci Ctr, Stockholm, Sweden..
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..ORCID iD: 0000-0002-0603-1241
Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.;Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA..
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2018 (English)In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 36, no 9, p. 865-+Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 36, no 9, p. 865-+
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Biological Sciences
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URN: urn:nbn:se:kth:diva-235603DOI: 10.1038/nbt.4226ISI: 000443986000029PubMedID: 30125269Scopus ID: 2-s2.0-85053078449OAI: oai:DiVA.org:kth-235603DiVA, id: diva2:1252150
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QC 20181001

Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2018-10-01Bibliographically approved

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