A Human Stem Cell-Derived Brain-Liver Chip for Assessing Blood-Brain-Barrier Permeation of Pharmaceutical Drugs.

Autor: Koenig L; TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany., Ramme AP; TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany., Faust D; TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany., Mayer M; Pharmacelsus GmbH, Science Park 2, 66123 Saarbrücken, Germany., Flötke T; Pharmacelsus GmbH, Science Park 2, 66123 Saarbrücken, Germany., Gerhartl A; Competence Unit Molecular Diagnostics, Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria., Brachner A; Competence Unit Molecular Diagnostics, Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria., Neuhaus W; Competence Unit Molecular Diagnostics, Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria.; Department of Medicine, Danube Private University, Steiner Landstraße 124, 3500 Krems an der Donau, Austria., Appelt-Menzel A; Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany.; Translational Center for Regenerative Therapies, Fraunhofer Institute for Silicate Research, Röntgenring 11, 97070 Würzburg, Germany., Metzger M; Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany.; Translational Center for Regenerative Therapies, Fraunhofer Institute for Silicate Research, Röntgenring 11, 97070 Würzburg, Germany., Marx U; TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany.; Department of Medical Biotechnology, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany., Dehne EM; TissUse GmbH, Oudenarder Str. 16, 13347 Berlin, Germany.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Oct 19; Vol. 11 (20). Date of Electronic Publication: 2022 Oct 19.
DOI: 10.3390/cells11203295
Abstrakt: 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-brain 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.
Databáze: MEDLINE
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