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

Maoz, Ben M. (author)
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.
Herland, Anna (author)
Karolinska Institutet,KTH,Mikro- och nanosystemteknik,Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Karolinska Inst, Dept Neurosci, Swedish Med Nanosci Ctr, Stockholm, Sweden.
FitzGerald, Edward A. (author)
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
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Grevesse, Thomas (author)
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.
Vidoudez, Charles (author)
Harvard Univ, Small Mol Mass Spectrometry Facil, Cambridge, MA 02138 USA.
Pacheco, Alan R. (author)
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA.;Boston Univ, Biol Design Ctr, Boston, MA 02215 USA.
Sheehy, Sean P. (author)
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.
Park, Tae-Eun (author)
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
Dauth, Stephanie (author)
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.
Mannix, Robert (author)
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.
Budnik, Nikita (author)
Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.
Shores, Kevin (author)
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.
Cho, Alexander (author)
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.
Nawroth, Janna C. (author)
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.
Segre, Daniel (author)
Boston Univ, Grad Program Bioinformat, Boston, MA 02215 USA.;Boston Univ, Biol Design Ctr, Boston, MA 02215 USA.;Boston Univ, Dept Phys, Dept Biomed Engn, Dept Biol, 590 Commonwealth Ave, Boston, MA 02215 USA.
Budnik, Bogdan (author)
Harvard Univ, Mass Spectrometry & Prote Resource Lab, Cambridge, MA 02138 USA.
Ingber, Donald E. (author)
Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.;Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.;Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
Parker, Kevin Kit (author)
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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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. Mikro- och nanosystemteknik (creator_code:org_t)
2018-10-01
2018
English.
In: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 36:9, s. 865-
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

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