A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-290375
- 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-brainSignificant 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.…
Autor(en): | Leopold Koenig, Anja Patricia Ramme, Daniel Faust, Manuela Mayer, Tobias Flötke, Anna Gerhartl, Andreas Brachner, Winfried Neuhaus, Antje Appelt-Menzel, Marco Metzger, Uwe Marx, Eva-Maria Dehne |
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URN: | urn:nbn:de:bvb:20-opus-290375 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cells |
ISSN: | 2073-4409 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 11 |
Heft / Ausgabe: | 20 |
Aufsatznummer: | 3295 |
Originalveröffentlichung / Quelle: | Cells (2022) 11:20, 3295. https://doi.org/10.3390/cells11203295 |
DOI: | https://doi.org/10.3390/cells11203295 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Freie Schlagwort(e): | blood-brain barrier (BBB) model; brain–liver chip; human induced pluripotent stem cells (hiPSCs); microphysiological systems (MPS); multi-organ chip |
Datum der Freischaltung: | 16.10.2023 |
Datum der Erstveröffentlichung: | 19.10.2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |