{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:48:13Z","timestamp":1788187693398,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"state and sponsored funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Numerous central nervous system pathological conditions involve blood\u2013brain barrier (BBB) disruption and the egress of immune cells in the brain. Controlling immune cell transmigration into the brain represents a potential therapeutic target. This study describes the application of a 3D human BBB spheroidal model that consists of six major brain cell types to test the transmigration of immune cells under normal and pathological conditions of inflammation and ischemia\u2013reperfusion injury (IRI). The cell types in the BBB organoid include brain microvascular endothelial cells (HBMVECs) and pericytes at the spheroids\u2019 surface, surrounding a core of astrocytes, microglia, oligodendrocytes, and neural progenitor cells. The model recapitulates the interaction of CD4+ T-cells and immunomodulators with HBMVECs at the BBB including changes in cell adhesion molecules expressed on their surface. This study demonstrated that the human 3D BBB model recapitulates many features of the barrier under normal and pathological conditions of inflammation and hypoxia-reperfusion injury. Proinflammatory cytokines and hypoxia disrupt the barrier and increase its permeability, decreasing the expression of tight junctions. Proinflammatory cytokines and reperfusion increase the expression of cell adhesion molecules and increase immune cell transmigration. Immune cell transmigration could be reduced with anti-cell adhesion molecule antibodies, further validating the model for studying neuroimmune interactions and for conducting high-throughput screening of therapeutic targets that modulate immune cell transmigration into the brain.<\/jats:p>","DOI":"10.3390\/cells15131173","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modeling Neuroimmunological Interactions at the Blood\u2013Brain Barrier Using In Vitro 3D Human Organoids: Inflammation and Ischemia\u2013Reperfusion Injury"],"prefix":"10.3390","volume":"15","author":[{"given":"Aya A.","family":"Eltaibany","sequence":"first","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"McGovern","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goodwell","family":"Nzou","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5689-431X","authenticated-orcid":false,"given":"Daniel","family":"Porada","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Seeds","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Atala","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12055","DOI":"10.1038\/s41598-019-48538-x","article-title":"Blockade of alpha4 integrins reduces leukocyte-endothelial interactions in cerebral vessels and improves memory in a mouse model of Alzheimer\u2019s disease","volume":"9","author":"Pietronigro","year":"2019","journal-title":"Sci. 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