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  - 
TY  - JOUR
A1  - Brachner, Andreas
A1  - Fragouli, Despina
A1  - Duarte, Iola F.
A1  - Farias, Patricia M. A.
A1  - Dembski, Sofia
A1  - Ghosh, Manosij
A1  - Barisic, Ivan
A1  - Zdzieblo, Daniela
A1  - Vanoirbeek, Jeroen
A1  - Schwabl, Philipp
A1  - Neuhaus, Winfried
T1  - Assessment of human health risks posed by nano-and microplastics is currently not feasible
JF  - International Journal of Environmental Research and Public Health
N2  - The exposure of humans to nano-and microplastic particles (NMPs) is an issue recognized as a potential health hazard by scientists, authorities, politics, non-governmental organizations and the general public. The concentration of NMPs in the environment is increasing concomitantly with global plastic production and the usage of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human samples, therefore necessitating a risk assessment of NMPs for human health. So far, a comprehensive risk assessment of NMPs is hampered by limited availability of appropriate reference materials, analytical obstacles and a lack of definitions and standardized study designs. Most studies conducted so far used polystyrene (PS) spheres as a matter of availability, although this polymer type accounts for only about 7% of total plastic production. Differently sized particles, different concentration and incubation times, and various biological models have been used, yielding hardly comparable data sets. Crucial physico-chemical properties of NMPs such as surface (charge, polarity, chemical reactivity), supplemented additives and adsorbed chemicals have been widely excluded from studies, although in particular the surface of NMPs determines the interaction with cellular membranes. In this manuscript we give an overview about the critical parameters which should be considered when performing risk assessments of NMPs, including novel reference materials, taking into account surface modifications (e.g., reflecting weathering processes), and the possible role of NMPs as a substrate and/or carrier for (pathogenic) microbes. Moreover, we make suggestions for biological model systems to evaluate immediate toxicity, long-term effects and the potential of NMPs to cross biological barriers. We are convinced that standardized reference materials and experimental parameters along with technical innovations in (nano)-particle sampling and analytics are a prerequisite for the successful realization of conclusive human health risk assessments of NMPs.
KW  - nanoplastics
KW  - nanoparticles
KW  - microplastics
KW  - microparticles
KW  - human exposure
KW  - biological barriers
KW  - biofilm
KW  - microbe carrier
KW  - toxicity
KW  - neurotoxicity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219423
SN  - 1660-4601
VL  - 17
IS  - 23
ER  -