| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cells, Vol 11, Iss 20, p 3295 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2073-4409 |
| DOI: |
10.3390/cells11203295 |
| Popis: |
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: |
Directory of Open Access Journals |
| Externí odkaz: |
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