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Ebola Hemorrhagic Shock Syndrome-on-a-Chip

Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models for Ebola hemorrhagic fever is a major obstacle that hinders the development of treatment strategies. Here, we model the Ebola hemorrh...

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Autores principales: Junaid, Abidemi, Tang, Huaqi, van Reeuwijk, Anne, Abouleila, Yasmine, Wuelfroth, Petra, van Duinen, Vincent, Stam, Wendy, van Zonneveld, Anton Jan, Hankemeier, Thomas, Mashaghi, Alireza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941864/
https://www.ncbi.nlm.nih.gov/pubmed/31887664
http://dx.doi.org/10.1016/j.isci.2019.100765
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author Junaid, Abidemi
Tang, Huaqi
van Reeuwijk, Anne
Abouleila, Yasmine
Wuelfroth, Petra
van Duinen, Vincent
Stam, Wendy
van Zonneveld, Anton Jan
Hankemeier, Thomas
Mashaghi, Alireza
author_facet Junaid, Abidemi
Tang, Huaqi
van Reeuwijk, Anne
Abouleila, Yasmine
Wuelfroth, Petra
van Duinen, Vincent
Stam, Wendy
van Zonneveld, Anton Jan
Hankemeier, Thomas
Mashaghi, Alireza
author_sort Junaid, Abidemi
collection PubMed
description Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models for Ebola hemorrhagic fever is a major obstacle that hinders the development of treatment strategies. Here, we model the Ebola hemorrhagic syndrome in a microvessel-on-a-chip system and demonstrate its applicability to drug studies. Luminal infusion of Ebola virus-like particles leads to albumin leakage from the engineered vessels. The process is mediated by the Rho/ROCK pathway and is associated with cytoskeleton remodeling. Infusion of Ebola glycoprotein (GP(1,2)) generates a similar phenotype, indicating the key role of GP(1,2) in this process. Finally, we measured the potency of a recently developed experimental drug FX06 and a novel drug candidate, melatonin, in phenotypic rescue. Our study confirms the effects of FX06 and identifies melatonin as an effective, safe, inexpensive therapeutic option that is worth investigating in animal models and human trials.
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spelling pubmed-69418642020-01-06 Ebola Hemorrhagic Shock Syndrome-on-a-Chip Junaid, Abidemi Tang, Huaqi van Reeuwijk, Anne Abouleila, Yasmine Wuelfroth, Petra van Duinen, Vincent Stam, Wendy van Zonneveld, Anton Jan Hankemeier, Thomas Mashaghi, Alireza iScience Article Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models for Ebola hemorrhagic fever is a major obstacle that hinders the development of treatment strategies. Here, we model the Ebola hemorrhagic syndrome in a microvessel-on-a-chip system and demonstrate its applicability to drug studies. Luminal infusion of Ebola virus-like particles leads to albumin leakage from the engineered vessels. The process is mediated by the Rho/ROCK pathway and is associated with cytoskeleton remodeling. Infusion of Ebola glycoprotein (GP(1,2)) generates a similar phenotype, indicating the key role of GP(1,2) in this process. Finally, we measured the potency of a recently developed experimental drug FX06 and a novel drug candidate, melatonin, in phenotypic rescue. Our study confirms the effects of FX06 and identifies melatonin as an effective, safe, inexpensive therapeutic option that is worth investigating in animal models and human trials. Elsevier 2019-12-12 /pmc/articles/PMC6941864/ /pubmed/31887664 http://dx.doi.org/10.1016/j.isci.2019.100765 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Junaid, Abidemi
Tang, Huaqi
van Reeuwijk, Anne
Abouleila, Yasmine
Wuelfroth, Petra
van Duinen, Vincent
Stam, Wendy
van Zonneveld, Anton Jan
Hankemeier, Thomas
Mashaghi, Alireza
Ebola Hemorrhagic Shock Syndrome-on-a-Chip
title Ebola Hemorrhagic Shock Syndrome-on-a-Chip
title_full Ebola Hemorrhagic Shock Syndrome-on-a-Chip
title_fullStr Ebola Hemorrhagic Shock Syndrome-on-a-Chip
title_full_unstemmed Ebola Hemorrhagic Shock Syndrome-on-a-Chip
title_short Ebola Hemorrhagic Shock Syndrome-on-a-Chip
title_sort ebola hemorrhagic shock syndrome-on-a-chip
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941864/
https://www.ncbi.nlm.nih.gov/pubmed/31887664
http://dx.doi.org/10.1016/j.isci.2019.100765
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