Format

Send to

Choose Destination
Nat Biotechnol. 2018 Oct;36(9):865-874. doi: 10.1038/nbt.4226. Epub 2018 Aug 20.

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

Author information

1
Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
2
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts, USA.
3
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
4
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
5
The Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel.
6
Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden.
7
Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
8
Small Molecule Mass Spectrometry Facility, Harvard University, Cambridge, Massachusetts, USA.
9
Graduate Program in Bioinformatics and Biological Design Center, Boston University, Boston, Massachusetts, USA.
10
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
11
Department of Biology, Department of Biomedical Engineering, Department of Physics, Boston University, Boston, Massachusetts, USA.
12
Mass Spectrometry and Proteomics Resource Laboratory, Harvard University, Cambridge, Massachusetts, USA.
13
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.

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.

PMID:
30125269
DOI:
10.1038/nbt.4226

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center