Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Sep;18(9):2838-2867.
doi: 10.1038/s41596-023-00861-4. Epub 2023 Aug 4.

Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration

You Jung Kang  1   2 , Yen N Diep  1   2   3 , Minh Tran  1   2   3 , Van Thi Ai Tran  1   2 , Ghuncha Ambrin  4 , Huyen Ngo  1   2   3 , Hansang Cho  5   6   7
Affiliations
Review

Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration

You Jung Kang et al. Nat Protoc. 2023 Sep.

Abstract

Neuroinflammation has either beneficial or detrimental effects, depending on risk factors and neuron-glia interactions in neurological disorders. However, studying neuroinflammation has been challenging due to the complexity of cell-cell interactions and lack of physio-pathologically relevant neuroinflammatory models. Here, we describe our three-dimensional microfluidic multicellular human neural culture model, referred to as a 'brain-on-a-chip' (BoC). This elucidates neuron-glia interactions in a controlled manner and recapitulates pathological signatures of the major neurological disorders: dementia, brain tumor and brain edema. This platform includes a chemotaxis module offering a week-long, stable chemo-gradient compared with the few hours in other chemotaxis models. Additionally, compared with conventional brain models cultured with mixed phenotypes of microglia, our BoC can separate the disease-associated microglia out of heterogeneous population and allow selective neuro-glial engagement in three dimensions. This provides benefits of interpreting the neuro-glia interactions while revealing that the prominent activation of innate immune cells is the risk factor leading to synaptic impairment and neuronal loss, validated in our BoC models of disorders. This protocol describes how to fabricate and implement our human BoC, manipulate in real time and perform end-point analyses. It takes 2 d to set up the device and cell preparations, 1-9 weeks to develop brain models under disease conditions and 2-3 d to carry out analyses. This protocol requires at least 1 month training for researchers with basic molecular biology techniques. Taken together, our human BoCs serve as reliable and valuable platforms to investigate pathological mechanisms involving neuroinflammation and to assess therapeutic strategies modulating neuroinflammation in neurological disorders.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kang, Y. J., Diep, Y. N., Tran, M. & Cho, H. Therapeutic targeting strategies for early- to late-staged Alzheimer’s disease. Int. J. Mol. Sci. 21, 9591 (2020). - PubMed - PMC
    1. Heneka, M. T. et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14, 388–405 (2015). - PubMed - PMC
    1. Park, J. et al. A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease. Nat. Neurosci. 21, 941–951 (2018). - PubMed - PMC
    1. Kinney, J. W. et al. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 4, 575–590 (2018).
    1. Tan, H.-Y., Cho, H. & Lee, L. P. Human mini-brain models. Nat. Biomed. Eng. 5, 11–25 (2021). - PubMed

Publication types

MeSH terms

LinkOut - more resources