Advances in microfluidic in vitro systems for neurological disease modeling

Abstract

Neurological disorders are the leading cause of disability and the second largest cause of death worldwide. Despite significant research efforts, neurology remains one of the most failure‐prone areas of drug development. The complexity of the human brain, boundaries to examining the brain directly in vivo, and the significant evolutionary gap between animal models and humans, all serve to hamper translational success. Recent advances in microfluidic in vitro models have provided new opportunities to study human cells with enhanced physiological relevance. The ability to precisely micro‐engineer cell‐scale architecture, tailoring form and function, has allowed for detailed dissection of cell biology using microphysiological systems (MPS) of varying complexities from single cell systems to “Organ‐on‐chip” models. Simplified neuronal networks have allowed for unique insights into neuronal transport and neurogenesis, while more complex 3D heterotypic cellular models such as neurovascular unit mimetics and “Organ‐on‐chip” systems have enabled new understanding of metabolic coupling and blood–brain barrier transport. These systems are now being developed beyond MPS toward disease specific micro‐pathophysiological systems, moving from “Organ‐on‐chip” to “Disease‐on‐chip.” This review gives an outline of current state of the art in microfluidic technologies for neurological disease research, discussing the challenges and limitations while highlighting the benefits and potential of integrating technologies. We provide examples of where such toolsets have enabled novel insights and how these technologies may empower future investigation into neurological diseases.

Publication DOI: https://doi.org/10.1002/jnr.24794
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: © 2021 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: Centre for Age‐related Medicine, Stavanger University Hospital, Stavanger, Norway; Alzheimer’s Research UK; Gerald Kerkut Charitable Trust; Royal Commission for the Exhibition of 1851; UK Research and Innovation
Uncontrolled Keywords: Alzheimer's,CNS,MPS,Parkinson's,organ-on-chip,stroke,Cellular and Molecular Neuroscience
Full Text Link:
Related URLs: https://onlinel ... .1002/jnr.24794 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2021-05
Published Online Date: 2021-02-13
Accepted Date: 2020-12-19
Authors: Holloway, Paul M.
Willaime‐Morawek, Sandrine
Siow, Richard
Barber, Melissa
Owens, Róisín M.
Sharma, Anup D.
Rowan, Wendy
Hill, Eric (ORCID Profile 0000-0002-9419-1500)
Zagnoni, Michele

Download

[img]

Version: Published Version

License: Creative Commons Attribution

| Preview

Export / Share Citation


Statistics

Additional statistics for this record