3D Organoid Assay of the Impact of Infected Erythrocyte Adhesion on the Blood-Brain Barrier.

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.