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Dev Dyn. 2019 Jan;248(1):65-77. doi: 10.1002/dvdy.24665. Epub 2018 Sep 12.

Compartmentalized Devices as Tools for Investigation of Human Brain Network Dynamics.

Author information

1
Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey.
2
Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey.
3
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey.
4
Department of Neuroscience and Cell Biology, Research Tower, Piscataway, New Jersey.
5
Pediatrics, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.

Abstract

Neuropsychiatric disorders have traditionally been difficult to study due to the complexity of the human brain and limited availability of human tissue. Induced pluripotent stem (iPS) cells provide a promising avenue to further our understanding of human disease mechanisms, but traditional 2D cell cultures can only provide a limited view of the neural circuits. To better model complex brain neurocircuitry, compartmentalized culturing systems and 3D organoids have been developed. Early compartmentalized devices demonstrated how neuronal cell bodies can be isolated both physically and chemically from neurites. Soft lithographic approaches have advanced this approach and offer the tools to construct novel model platforms, enabling circuit-level studies of disease, which can accelerate mechanistic studies and drug candidate screening. In this review, we describe some of the common technologies used to develop such systems and discuss how these lithographic techniques have been used to advance our understanding of neuropsychiatric disease. Finally, we address other in vitro model platforms such as 3D culture systems and organoids and compare these models with compartmentalized models. We ask important questions regarding how we can further harness iPS cells in these engineered culture systems for the development of improved in vitro models. Developmental Dynamics 248:65-77, 2019.

KEYWORDS:

3D culture; Huntington's Disease; axonal transport; compartmentalization; induced neurons; microfluidics; neurocircuitry; neuropsychiatric disorders; organoids; stem cells

PMID:
30117633
PMCID:
PMC6312734
[Available on 2020-01-01]
DOI:
10.1002/dvdy.24665
[Indexed for MEDLINE]

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