{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:02:29Z","timestamp":1791496949238,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Ministry for Education and Research BMBF","award":["01EK1608E"],"award-info":[{"award-number":["01EK1608E"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood\u2013brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier.<\/jats:p>","DOI":"10.3390\/cells11203295","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T20:32:23Z","timestamp":1666211543000},"page":"3295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["A Human Stem Cell-Derived Brain-Liver Chip for Assessing Blood-Brain-Barrier Permeation of Pharmaceutical Drugs"],"prefix":"10.3390","volume":"11","author":[{"given":"Leopold","family":"Koenig","sequence":"first","affiliation":[{"name":"TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja Patricia","family":"Ramme","sequence":"additional","affiliation":[{"name":"TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Faust","sequence":"additional","affiliation":[{"name":"TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Mayer","sequence":"additional","affiliation":[{"name":"Pharmacelsus GmbH, Science Park 2, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Fl\u00f6tke","sequence":"additional","affiliation":[{"name":"Pharmacelsus GmbH, Science Park 2, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gerhartl","sequence":"additional","affiliation":[{"name":"Competence Unit Molecular Diagnostics, Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-8561","authenticated-orcid":false,"given":"Andreas","family":"Brachner","sequence":"additional","affiliation":[{"name":"Competence Unit Molecular Diagnostics, Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-7183","authenticated-orcid":false,"given":"Winfried","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Competence Unit Molecular Diagnostics, Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria"},{"name":"Department of Medicine, Danube Private University, Steiner Landstra\u00dfe 124, 3500 Krems an der Donau, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Appelt-Menzel","sequence":"additional","affiliation":[{"name":"Chair of Tissue Engineering and Regenerative Medicine, University Hospital W\u00fcrzburg, R\u00f6ntgenring 11, 97070 W\u00fcrzburg, Germany"},{"name":"Translational Center for Regenerative Therapies, Fraunhofer Institute for Silicate Research, R\u00f6ntgenring 11, 97070 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metzger","sequence":"additional","affiliation":[{"name":"Chair of Tissue Engineering and Regenerative Medicine, University Hospital W\u00fcrzburg, R\u00f6ntgenring 11, 97070 W\u00fcrzburg, Germany"},{"name":"Translational Center for Regenerative Therapies, Fraunhofer Institute for Silicate Research, R\u00f6ntgenring 11, 97070 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-138X","authenticated-orcid":false,"given":"Uwe","family":"Marx","sequence":"additional","affiliation":[{"name":"TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany"},{"name":"Department of Medical Biotechnology, Institute of Biotechnology, Technische Universit\u00e4t Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Dehne","sequence":"additional","affiliation":[{"name":"TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1038\/srep04160","article-title":"A Retinoic Acid-Enhanced, Multicellular Human Blood-Brain Barrier Model Derived from Stem Cell Sources","volume":"4","author":"Lippmann","year":"2015","journal-title":"Sci. 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