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Human BBB-on-a-chip reveals barrier disruption, endothelial inflammation, and T cell migration under neuroinflammatory conditions

Leiden, September 14, 2023 – MIMETAS Scientists established a high-throughput human BBB-on-a-chip to study neuroinflammation and transendothelial migration.

The blood-brain barrier (BBB) serves as a physiological and metabolic barrier that ensures a homeostatic environment for a healthy functioning of the central nervous system (CNS). This protective function of the BBB is challenged in neurological conditions, such as stroke and multiple sclerosis (MS), resulting in neuroinflammation, which in turn exacerbates disease progression. To investigate neuroinflammatory disorders, researchers have traditionally relied on animal models and transwell-based blood-brain barrier (BBB) models. Recapitulation of the intricate pathogenesis, clinical evolution, and disease variability seen in patients has consistently posed a challenge when using those traditional models. To bridge this gap and achieve a closer mimicry of human disease progression, more advanced in vitro microfluidic models, such as our innovative 3D tissue models, offer a promising solution.

In this work, MIMETAS scientists developed a human BBB-on-a-chip to study neuroinflammation and transendothelial migration (TEM). This model comprises of primary human brain microvascular endothelial cells (HBMECs) cultivated under bidirectional perfusion. To mimic an inflammatory environment, pro-inflammatory cytokines were used. The researchers found that exposure to these cytokines led to a concentration-dependent disruption of the BBB. Furthermore, it induced noticeable alterations in the morphology of endothelial cells. Notably, the researchers also found an upregulation in the expression of critical cell adhesion molecules, ICAM-1 and VCAM-1 by HBMECs. An augmented migration of T cells into the basolateral compartment was also observed in response to these inflammatory conditions. The study further shows that T cell adhesion and migration was decreased in the presence of Natalizumab, an anti-VLA4 monoclonal antibody that is used to treat MS.

Taken together, the development of this high-throughput, membrane-free microfluidic BBB-on-a-chip model provides a valuable tool for studying neuroinflammation and the evaluation of potential therapeutic strategies. Its advanced imaging capabilities also make it ideal for investigating drug candidates aimed at reducing immune cell infiltration and facilitating BBB restoration.

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