TY  - JOUR
A1  - Koenig, Leopold
A1  - Ramme, Anja Patricia
A1  - Faust, Daniel
A1  - Mayer, Manuela
A1  - Flötke, Tobias
A1  - Gerhartl, Anna
A1  - Brachner, Andreas
A1  - Neuhaus, Winfried
A1  - Appelt-Menzel, Antje
A1  - Metzger, Marco
A1  - Marx, Uwe
A1  - Dehne, Eva-Maria
T1  - A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs
JF  - Cells
N2  - 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.
KW  - blood-brain barrier (BBB) model
KW  - human induced pluripotent stem cells (hiPSCs)
KW  - microphysiological systems (MPS)
KW  - multi-organ chip
KW  - brain–liver chip
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290375
SN  - 2073-4409
VL  - 11
IS  - 20
ER  -