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The effect of lung tumor cluster-derived extracellular vesicles on the integrity of a mono- and multi-layered vessel on a chip model

Loenen, N.A. van (2023) The effect of lung tumor cluster-derived extracellular vesicles on the integrity of a mono- and multi-layered vessel on a chip model.

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Abstract:Lung cancer is characterised by a high rate of mortality and metastasis. Lately, extracellular vesicles (EVs) have gained attention as key players in preparing the pre-metastatic niche (PMN) by promoting vascular leakage. Vessel-on-a-chip (VoC) models are efficient and involve human physiological components that give more insights in the mechanism of vascular leakage. Using viscous finger patterning (VFP), renowned as a simple and reproducible technique, cylindrical mono- and multilayered vessels can be created. Also the uprise of microfluidic devices allows the application of flow inside VoCs. With the ability to more and more accurately mimic a physically correct human blood vessel, research on effect of EVs could be conducted with higher reliability. In this study, an optimized VFP method was used for the patterning of both mono- and multi-layered VoCs. To study the effect of EVs, lung tumor clusters were prepared and the tumor-conditioned medium was filtered to only obtain the tumor-derived EVs (tdEVs). To test the permeability of the formed VoCs, the vessels were stimulated with either EVs or a positive control being TNF-α or negative control being plain medium for deterioration of integrity. After this experiment, immunostaining for tight junctions was conducted to analyse the integrity of the vessel barriers. This way, the possible promotion of vascular leakage by tdEVs could be indicated. As a pilot experiment, the VoCs were also subjected to a flow to analyse the cell alignment under these conditions. Although the outcomes of this research were inconclusive regarding the isolation and effect of EVs on VoCs, further research on EVs using more complex organ-on-a-chip models for different mechanisms underlying PMN formation could show great potential for the prevention and treatment of metastatic tumors.
Item Type:Essay (Bachelor)
Faculty:TNW: Science and Technology
Subject:42 biology, 44 medicine
Programme:Biomedical Technology BSc (56226)
Link to this item:https://purl.utwente.nl/essays/97119
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