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Molecular Neurobiology

, Volume 56, Issue 12, pp 8489–8512 | Cite as

Microfluidic Brain-on-a-Chip: Perspectives for Mimicking Neural System Disorders

  • Mirza Ali Mofazzal Jahromi
  • Amir Abdoli
  • Mohammad Rahmanian
  • Hassan Bardania
  • Mehrdad Bayandori
  • Seyed Masoud Moosavi Basri
  • Alireza Kalbasi
  • Amir Reza Aref
  • Mahdi KarimiEmail author
  • Michael R HamblinEmail author
Article

Abstract

Neurodegenerative diseases (NDDs) include more than 600 types of nervous system disorders in humans that impact tens of millions of people worldwide. Estimates by the World Health Organization (WHO) suggest NDDs will increase by nearly 50% by 2030. Hence, development of advanced models for research on NDDs is needed to explore new therapeutic strategies and explore the pathogenesis of these disorders. Different approaches have been deployed in order to investigate nervous system disorders, including two-and three-dimensional (2D and 3D) cell cultures and animal models. However, these models have limitations, such as lacking cellular tension, fluid shear stress, and compression analysis; thus, studying the biochemical effects of therapeutic molecules on the biophysiological interactions of cells, tissues, and organs is problematic. The microfluidic “organ-on-a-chip” is an inexpensive and rapid analytical technology to create an effective tool for manipulation, monitoring, and assessment of cells, and investigating drug discovery, which enables the culture of various cells in a small amount of fluid (10−9 to 10−18 L). Thus, these chips have the ability to overcome the mentioned restrictions of 2D and 3D cell cultures, as well as animal models. Stem cells (SCs), particularly neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) have the capability to give rise to various neural system cells. Hence, microfluidic organ-on-a-chip and SCs can be used as potential research tools to study the treatment of central nervous system (CNS) and peripheral nervous system (PNS) disorders. Accordingly, in the present review, we discuss the latest progress in microfluidic brain-on-a-chip as a powerful and advanced technology that can be used in basic studies to investigate normal and abnormal functions of the nervous system.

Keywords

Nervous system Brain Neurodegenerative diseases Microfluidic brain-on-a-chip Stem cells 

Abbreviations

2D

two-dimensional

3D

three-dimensional

AD

Alzheimer’s disease

ADME

adsorption, distribution, metabolism, excretion

ALT

amyotrophic lateral sclerosis

ASTs

astrocytes

BBB

blood–brain barrier

BECs

brain endothelial cells

bFGF

basic fibroblast growth factor

BMECs

brain microvascular endothelial cells

BRAIN

Brain Research through Advancing Innovative Neurotechnologies

CD

cluster of differentiation

CNS

central nervous system

CTIP2

chicken ovalbumin upstream promoter transcription factor-interacting protein 2

DARPA

Defense Advanced Research Projects Agency

DCX

doublecortin

DOX

doxorubicin

ECM

extracellular matrix

ECs

endothelial cells

EGCs

embryonic germ cells

EGFR

epidermal growth factor receptor

EGFR

epidermal growth factor

ESCs

embryonic stem cells

FDA

Food and Drug Administration

FITC

fluorescein isothiocyanate

FOXG1

forkhead box protein G1

GBM

glioblastoma multiforme

G-CSF

granulocyte colony-stimulating factor

GFAP

glial fibrillary acidic protein

hBMVECs

human brain microvascular endothelial cells

HBP

Human Brain Project

HD

Huntington’s disease

hiPSCs

human-induced pluripotent stem cells

HUVEC

human umbilical vein endothelial cells

ISL1

insulin gene enhancer protein 1

ITSS

insulin-transferrin–sodium selenite supplement

IL-6

interleukin-6

KROX20

early growth response 2 (egr2)

LOC

laboratory-on-a-chip

LPS

lipopolysaccharide

MS

multiple sclerosis

NCATS

National Center for Advancing Translational Sciences

NDDs

neurodegenerative diseases

NIH

National Institutes of Health

NPCs

neural progenitor cells

NSCs

neural stem cells

NSF

National Science Foundation

NG2

neuron glial antigen 2

NSPCs

neural stem/progenitor cells

NVC

neurovascular chip

PD

Parkinson’s disease

PAX2/6

paired box gene 2/6

PDMS

polydimethylsiloxane

PEGDA

poly(ethylene) glycol diacrylate

Pgp

P-glycoprotein

PNS

peripheral nervous system

PTEF

polytetrafluoroethylene

PTEN

phosphatase and tensin homolog

RT-PCR

real-time polymerase chain reaction

SCs

stem cells

SCZ

schizophrenia

SEM

scanning electron microscopy

SOX2

sex determining region Y-box 2

SSEA

stage-specific embryonic antigen

TBI

traumatic brain injury

TBR1

T-box brain 1

TEER

trans-endothelial electrical resistance

TNF-α

tumor necrosis factor-alpha

TUJ1

neuron-specific class III beta-tubulin

TUNEL

terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling

ZO-1

zonula occludens-1; GFP, green fluorescent protein; human cerebral microvascular endothelial cell, hCMEC/D3; human umbilical veinendothelial cell, HUVEC.

Notes

Funding

M.R.H. was supported by US NIH Grants R01AI050875 and R21AI121700.

Compliance with Ethical Standards

Competing Interests

M.R.H. is on the following Scientific Advisory Boards:

Transdermal Cap Inc., Cleveland, OH.

BeWell Global Inc., Wan Chai, Hong Kong.

Hologenix Inc., Santa Monica, CA.

LumiThera Inc., Poulsbo, WA.

Vielight, Toronto, Canada.

Bright Photomedicine, Sao Paulo, Brazil.

Quantum Dynamics LLC, Cambridge, MA.

Global Photon Inc., Bee Cave, TX.

Medical Coherence, Boston MA.

NeuroThera, Newark DE.

JOOVV Inc., Minneapolis–St. Paul, MN.

AIRx Medical, Pleasanton, CA.

FIR Industries, Inc. Ramsey, NJ.

UVLRx Therapeutics, Oldsmar, FL.

Ultralux UV Inc., Lansing MI.

Illumiheal & Petthera, Shoreline, WA.

MB Lasertherapy, Houston, TX.

ARRC LED, San Clemente, CA.

Varuna Biomedical Corp., Incline Village, NV.

Niraxx Light Therapeutics, Inc., Boston, MA.

M.R.H. has been a consultant for:

Lexington Int, Boca Raton, FL.

USHIO Corp, Japan.

Merck KGaA, Darmstadt, Germany.

Philips Electronics Nederland B.V.

Johnson & Johnson Inc., Philadelphia, PA.

Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.

M.R.H. is a stockholder in:

Global Photon Inc., Bee Cave, TX.

Mitonix, Newark, DE.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mirza Ali Mofazzal Jahromi
    • 1
    • 2
  • Amir Abdoli
    • 2
    • 3
    • 4
  • Mohammad Rahmanian
    • 2
    • 5
  • Hassan Bardania
    • 6
  • Mehrdad Bayandori
    • 7
    • 8
  • Seyed Masoud Moosavi Basri
    • 9
  • Alireza Kalbasi
    • 10
  • Amir Reza Aref
    • 11
  • Mahdi Karimi
    • 7
    • 8
    • 12
    • 13
    • 14
    Email author
  • Michael R Hamblin
    • 14
    • 15
    • 16
    Email author
  1. 1.Department of Advanced Medical Sciences & Technologies, School of MedicineJahrom University of Medical SciencesJahromIran
  2. 2.Research Center for Noncommunicable Diseases, School of MedicineJahrom University of Medical SciencesJahromIran
  3. 3.Department of Parasitology and Mycology, School of MedicineJahrom University of Medical SciencesJahromIran
  4. 4.Zoonoses Research CenterJahrom University of Medical SciencesJahromIran
  5. 5.Department of Anesthesiology, Critical Care, and Pain MedicineJahrom University of Medical SciencesJahromIran
  6. 6.Cellular and Molecular Research CenterYasuj University of Medical SciencesYasujIran
  7. 7.Oncopathology Research CenterIran University of Medical SciencesTehranIran
  8. 8.Department of Medical Nanotechnology, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran
  9. 9.Civil & Environmental Engineering DepartmentShahid Beheshti UniversityTehranIran
  10. 10.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  11. 11.Department of Cancer Biology, Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Department of GeneticsHarvard Medical SchoolBostonUSA
  12. 12.Cellular and Molecular Research CenterIran University of Medical SciencesTehranIran
  13. 13.Research Center for Science and Technology in MedicineTehran University of Medical SciencesTehranIran
  14. 14.Wellman Center for Photomedicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  15. 15.Department of DermatologyHarvard Medical SchoolBostonUSA
  16. 16.Harvard-MIT Division of Health Sciences and TechnologyCambridgeUSA

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