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In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption
Published on: June 20, 2017
3D Organoid Assay of the Impact of Infected Erythrocyte Adhesion on the Blood-Brain Barrier
Yvonne Adams1, Anja Ramstedt Jensen2
1Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. yadams@sund.ku.dk.
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.
Insights
Cerebral malaria (CM) involves Plasmodium falciparum parasites blocking brain vessels. Researchers developed a 3D human blood-brain barrier model for high-throughput analysis of parasite effects on brain tissue.
Area of Science:
- Neuroscience
- Infectious Diseases
- Cell Biology
Background:
- Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection.
- Parasite sequestration in brain microvasculature causes inflammation, occlusion, and swelling.
- Previous studies used limited single-cell, monolayer assays to model the human blood-brain barrier (BBB).
Purpose of the Study:
- To develop and validate a novel 3D human-derived model of the blood-brain barrier (BBB).
- To investigate the effects of Plasmodium falciparum infected erythrocytes (IEs) on the BBB in a more physiologically relevant system.
- To enable high-throughput analysis of CM pathogenesis.
Main Methods:
- Constructed a 3D human BBB organoid model using endothelial cells, pericytes, and astrocytes.
- Demonstrated self-assembly and scalability of the organoids in 96-well plates.
- Utilized the organoid model to assess parasite adhesion, barrier function, and morphological changes.
Main Results:
- The 3D BBB organoid model successfully recapitulates key cellular interactions of the human BBB.
- The model allows for direct assessment of Plasmodium falciparum infected erythrocyte adhesion to the BBB.
- The organoids enable analysis of BBB integrity and structural changes upon parasite exposure.
Conclusions:
- A novel, human-derived 3D BBB organoid model offers a powerful tool for studying cerebral malaria.
- This high-throughput model advances the investigation of parasite-host interactions at the BBB.
- The model facilitates a deeper understanding of CM pathophysiology and potential therapeutic targets.
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