{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:52:43Z","timestamp":1780318363858,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The blood\u2013brain barrier (BBB) regulates the interaction between the highly vulnerable central nervous system (CNS) and the peripheral parts of the body. Disruption of the BBB has been associated with multiple neurological disorders, in which immune pathways in microglia are suggested to play a key role. Currently, many in vitro BBB model systems lack a physiologically relevant microglia component in order to address questions related to the mechanism of BBB integrity or the transport of molecules between the periphery and the CNS. To bridge this gap, we redefined a serum-free medium in order to allow for the successful co-culturing of human inducible pluripotent stem cell (hiPSC)-derived microglia and hiPSC-derived brain microvascular endothelial-like cells (BMECs) without influencing barrier properties as assessed by electrical resistance. We demonstrate that hiPSC-derived microglia exposed to lipopolysaccharide (LPS) weaken the barrier integrity, which is associated with the secretion of several cytokines relevant in neuroinflammation. Consequently, here we provide a simplistic humanised BBB model of neuroinflammation that can be further extended (e.g., by addition of other cell types in a more complex 3D architecture) and applied for mechanistic studies and therapeutic compound profiling.<\/jats:p>","DOI":"10.3390\/cells11030419","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T11:02:53Z","timestamp":1643194973000},"page":"419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Generation of an hiPSC-Derived Co-Culture System to Assess the Effects of Neuroinflammation on Blood\u2013Brain Barrier Integrity"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8689-4783","authenticated-orcid":false,"given":"Daniel","family":"Bull","sequence":"first","affiliation":[{"name":"ARUK UCL Drug Discovery Institute, University College London, London WC1E 6BT, UK"},{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-3025","authenticated-orcid":false,"given":"Colette","family":"Bichsel","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences and The Roche Institute for Translational Bioengineering, Roche Innovation Center Basel, 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6151-4257","authenticated-orcid":false,"given":"Markus","family":"Britschgi","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-0801","authenticated-orcid":false,"given":"Simon","family":"Gutbier","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/apha.12250","article-title":"The neurovascular unit\u2014Concept review","volume":"210","author":"Muoio","year":"2014","journal-title":"Acta Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/pr.57.2.4","article-title":"The blood-brain barrier\/neurovascular unit in health and disease","volume":"57","author":"Hawkins","year":"2005","journal-title":"Pharmacol. 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