Title Assessment of barrier integrity in a glial cell-based model using teer-integrated organ-on-chip technology
Translation of Title Barjero vientisumo vertinimas glijos ląstelių pagrindu sukurtame modelyje, naudojant organo-ant-lusto technologiją su integruota TEER matavimo sistema.
Authors Jašinskaitė, Eglė
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Pages 71
Keywords [eng] Organ-on-chip, C6 glioma cells, Calcium Chelation, TEER, CNS, BBB, EDTA, Dexamethasone, Barrier, Integrity, Barrier modulation
Abstract [eng] Dementia affects 55 million people worldwide with projections reaching 139 million by 2050, Parkinson's disease prevalence surged by 274% between 1990 and 2021, and conditions such as ALS, multiple sclerosis, and glioblastoma collectively affect millions more. One similarity across many of these conditions is dysfunction of the blood-brain barrier (BBB), which simultaneously contributes to disease pathology and restricts therapeutic drug deliver. This dual challenge is reflected in the consistently poor performance of CNS drug candidates in clinical trials: approvals occur at less than half the rate of non-CNS drugs. One of main causes is the failure of current biomedical models to replicate the complexity of the human CNS barrier. Organ-on-Chip (OOC) technology and microflu-idic systems can bridge this gap, enabling more physiologically relevant in vitro modelling of barrier dynamics. To investigate barrier-specific properties in such systems, the ability to reversibly modulate barrier integrity and validate the modulation with an established metric, such as transepitheli-al/endothelial electrical resistance (TEER), is crucial. The present work addresses this need by devel-oping a rat glial cell-based OOC model with integrated TEER measurement and controlled barrier modulation capability. The involvement of intercellular junctions in barrier integrity and cell-cell communication sug-gested that targeting them should open the doors for barrier modulation. After overview of the mecha-nism involving calcium in barrier integrity, ethylenediaminetetraacetic acid (EDTA) was chosen as a modulator of the barrier integrity to create a low integrity barrier state, while dexamethasone was chosen to increase barrier integrity creating a high integrity barrier state. The study showed that the integrated PVD microelectrode OOC system successfully achieved TEER measurements within the physiologically interpretable range. Also, it confirmed the possibility of establishing two pharmacologically distinct barrier states in the C6 OOC model: a high-integrity state under dexamethasone conditioning and a low-integrity state following EDTA treatment. Lastly, it showed that calcium chelation by EDTA functioned as an effective and reproducible switch for barrier integrity in the C6 glial OOC model.
Dissertation Institution Vilniaus universitetas.
Type Master thesis
Language English
Publication date 2026