ICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation

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dc.authorid0000-0002-5726-1928
dc.authorid0000-0002-5685-3737
dc.authorid0000-0003-0690-5575
dc.authorid0000-0002-8126-0490
dc.authorid0000-0002-4470-6641
dc.authorid0000-0001-8251-4520
dc.authorid0000-0003-4509-2212
dc.contributor.authorSaglam Metiner, Pelin
dc.contributor.authorYanasik, Sena
dc.contributor.authorOdabasi, Yusuf Caglar
dc.contributor.authorModamio, Jennifer
dc.contributor.authorNegwer, Moritz
dc.contributor.authorBiray Avci, Cigir
dc.contributor.authorYesil Celiktas, Ozlem
dc.date.accessioned2025-02-24T12:26:12Z
dc.date.available2025-02-24T12:26:12Z
dc.date.issued2024
dc.departmentEge Üniversitesi, Mühendislik Fakültesi, Biyomühendislik Bölümü
dc.description.abstractPropofol and midazolam are the current standard of care for prolonged sedation in Intensive Care Units (ICUs). However, the effects and mechanism of these sedatives in brain tissue are unclear. Herein, the development of an ICU patient-on-a-chip platform to elucidate those effects is reported. The humanized neural tissue compartment combines mast cells differentiated from human induced pluripotent stem cells (hiPSCs) with cerebral organoids in a three-dimensional (3D) matrix, which is covered with a membrane populated with human cerebral microvascular endothelial cells (hCMEC/D3) that separates the tissue chamber from the vascular lumen, where sedatives were infused for four days to evaluate neurotoxicity and cell-mediated immune responses. Subsequent to propofol administration, gene expressions of CD40 and TNF-alpha in mast cells, AIF1 in microglia and GFAP/S100B/OLIG2/MBP in macroglia were elevated, as well as NOS2, CD80, CD40, CD68, IL6 and TNF-alpha mediated proinflammation is noted in cerebral organoids, which resulted in higher expressions of GJB1, GABA-A and NMDAR1 in the tissue construct of the platform. Besides, midazolam administration stimulated expression of CD40 and CD203c+ reactivated mast cell proliferation and compromised BBB permeability and decreased TEER values with higher barrier disruption, whereas increased populations of CD11b+ microglia, higher expressions of GFAP/DLG4/GJB1 and GABA-A-/NMDAR1- identities, as well as glutamate related neurotoxicity and IL1B, IFNG, IFNA1, IL6 genes mediated proinflammation, resulting in increased apoptotic zones are observed in cerebral organoids. These results suggest that different sedatives cause variations in cell type activation that modulate different pathways related to neuroinflammation and neurotoxicity in the ICU patient-on-chip platform.
dc.identifier.citationSaglam-Metiner, P., Yanasik, S., Odabasi, Y. C., Modamio, J., Negwer, M., Biray-Avci, C., Guler, A., Erturk, A., Yildirim, E., & Yesil-Celiktas, O. (2024). ICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation. Communications Biology, 7(1), 1627-19.
dc.identifier.doi10.1038/s42003-024-07313-z
dc.identifier.endpage19
dc.identifier.issn2399-3642
dc.identifier.issue1
dc.identifier.pmid39639082
dc.identifier.scopus2-s2.0-85211377268
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1038/s42003-024-07313-z
dc.identifier.urihttps://hdl.handle.net/11454/116184
dc.identifier.volume7
dc.identifier.wosWOS:001371018600001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorSaglam Metiner, Pelin
dc.institutionauthorYanasik, Sena
dc.institutionauthorOdabasi, Yusuf Caglar
dc.institutionauthorBiray Avci, Cigir
dc.institutionauthorYesil Celiktas, Ozlem
dc.institutionauthorid0000-0002-5726-1928
dc.institutionauthorid0000-0002-5685-3737
dc.institutionauthorid0000-0003-0690-5575
dc.institutionauthorid0000-0001-8251-4520
dc.institutionauthorid0000-0003-4509-2212
dc.language.isoen
dc.publisherNature Portfolio
dc.relation.ispartofCommunications Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectdown-regulatıon
dc.subjectt-cells
dc.subjectpropofol
dc.subjectdifferentiation
dc.subjectcolocalization
dc.subjectdegranulation
dc.subjectinhibition
dc.subjectactivation
dc.subjectmidazolam
dc.titleICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation
dc.typeArticle

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