Abstract
Mass sequestration of Plasmodium falciparum parasites in the brain microvasculature can lead to cerebral malaria (CM), characterized by inflammation, vessel occlusion, and brain swelling. To date, only single-cell-type, monolayer assays have been used to investigate the effect of infected erythrocytes (IEs) on the human blood–brain barrier (BBB) and the underlying parenchyma. Here we present a human-derived 3D model of the BBB comprised of endothelial cells, pericytes, and astrocytes in direct contact with each other. The organoids readily self-assemble and can easily be grown in 96-well plates, allowing for high-throughput analysis. These organoids allow for the assessment of parasite adhesion, and analysis of barrier function, and gross morphological changes in response to parasite exposure.
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Acknowledgments
This work was supported by Lundbeckfonden (R180-2014-3098 and R313-2019-322) and the Danish Council for Independent Research (8020-00034B).
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Adams, Y., Jensen, A.R. (2022). 3D Organoid Assay of the Impact of Infected Erythrocyte Adhesion on the Blood–Brain Barrier. In: Jensen, A.T.R., Hviid, L. (eds) Malaria Immunology. Methods in Molecular Biology, vol 2470. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2189-9_44
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DOI: https://doi.org/10.1007/978-1-0716-2189-9_44
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