Using organ-on-a-chip technology to study haemorrhagic activities of snake venoms on endothelial tubules.

Autor: Bittenbinder MA; Naturalis Biodiversity Center, 2333 CR, Leiden, The Netherlands.; AIMMS, Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV, Amsterdam, The Netherlands., Bonanini F; Mimetas, Leiden, The Netherlands., Kurek D; Mimetas, Leiden, The Netherlands., Vulto P; Mimetas, Leiden, The Netherlands., Kool J; AIMMS, Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV, Amsterdam, The Netherlands. j.kool@vu.nl., Vonk FJ; Naturalis Biodiversity Center, 2333 CR, Leiden, The Netherlands.; AIMMS, Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081HV, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jun 04; Vol. 14 (1), pp. 11157. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1038/s41598-024-60282-5
Abstrakt: Snakebite envenomation is a major public health issue which causes severe morbidity and mortality, affecting millions of people annually. Of a diverse range of clinical manifestations, local and systemic haemorrhage are of particular relevance, as this may result in ischemia, organ failure and even cardiovascular shock. Thus far, in vitro studies have failed to recapitulate the haemorrhagic effects observed in vivo. Here, we present an organ-on-a-chip approach to investigate the effects of four different snake venoms on a perfused microfluidic blood vessel model. We assess the effect of the venoms of four snake species on epithelial barrier function, cell viability, and contraction/delamination. Our findings reveal two different mechanisms by which the microvasculature is being affected, either by disruption of the endothelial cell membrane or by delamination of the endothelial cell monolayer from its matrix. The use of our blood vessel model may shed light on the key mechanisms by which tissue-damaging venoms exert their effects on the capillary vessels, which could be helpful for the development of effective treatments against snakebites.
(© 2024. The Author(s).)
Databáze: MEDLINE
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