posted on 2017-11-12, 00:00authored byJannick Theobald, Ali Ghanem, Patrick Wallisch, Amin A. Banaeiyan, Miguel A. Andrade-Navarro, Katerina Taškova, Manuela Haltmeier, Andreas Kurtz, Holger Becker, Stefanie Reuter, Ralf Mrowka, Xinlai Cheng, Stefan Wölfl
Advances
in organ-on-chip technologies for the application in in
vitro drug development provide an attractive alternative approach
to replace ethically controversial animal testing and to establish
a basis for accelerated drug development. In recent years, various
chip-based tissue culture systems have been developed, which are mostly
optimized for cultivation of one single cell type or organoid structure
and lack the representation of multi organ interactions. Here we present
an optimized microfluidic chip design consisting of interconnected
compartments, which provides the possibility to mimic the exchange
between different organ specific cell types and enables to study interdependent
cellular responses between organs and demonstrate that such tandem
system can greatly improve the reproducibility and efficiency of toxicity
studies. In a simplified liver-kidney-on-chip model, we showed that
hepatic cells that grow in microfluidic conditions abundantly and
stably expressed metabolism-related biomarkers. Moreover, we applied
this system for investigating the biotransformation and toxicity of
Aflatoxin B1 (AFB1) and Benzoalphapyrene (BαP), as well as the
interaction with other chemicals. The results clearly demonstrate
that the toxicity and metabolic response to drugs can be evaluated
in a flow-dependent manner within our system, supporting the importance
of advanced interconnected multiorgans in microfluidic devices for
application in in vitro toxicity testing and as optimized tissue culture
systems for in vitro drug screening.