title: A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture.
abstract: Current in vitro and animal tests for drug development are failing to emulate the systemic organ complexity of the human body and, therefore, to accurately predict drug toxicity. In this study, we present a multi-organ-chip capable of maintaining 3D tissues derived from cell lines, primary cells and biopsies of various human organs. We designed a multi-organ-chip with co-cultures of human artificial liver microtissues and skin biopsies, each a (1)/100,000 of the biomass of their original human organ counterparts, and have successfully proven its long-term performance. The system supports two different culture modes: i) tissue exposed to the fluid flow, or ii) tissue shielded from the underlying fluid flow by standard Transwell® cultures. Crosstalk between the two tissues was observed in 14-day co-cultures exposed to fluid flow. Applying the same culture mode, liver microtissues showed sensitivity at different molecular levels to the toxic substance troglitazone during a 6-day exposure. Finally, an astonishingly stable long-term performance of the Transwell®-based co-cultures could be observed over a 28-day period. This mode facilitates exposure of skin at the air-liquid interface. Thus, we provide here a potential new tool for systemic substance testing.
authors: Technische Universität Berlin, Institute of Biotechnology, Department of Medical Biotechnology, Gustav-Meyer-Allee 25, Germany. ilka.wagner@tu-berlin.de
authors: Ilka
authors: I
authors: Wagner
authors: Eva-Maria
authors: EM
authors: Materne
authors: Sven
authors: S
authors: Brincker
authors: Ute
authors: U
authors: Süssbier
authors: Caroline
authors: C
authors: Frädrich
authors: Mathias
authors: M
authors: Busek
authors: Frank
authors: F
authors: Sonntag
authors: Dmitry A
authors: DA
authors: Sakharov
authors: Evgeny V
authors: EV
authors: Trushkin
authors: Alexander G
authors: AG
authors: Tonevitsky
authors: Roland
authors: R
authors: Lauster
authors: Uwe
authors: U
authors: Marx
mesh_terms: D018533:Biomass; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000633:toxicity; D018920:Coculture Techniques / Q000295:instrumentation*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D012313:RNA / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones / Q000633:toxicity; D046509:Tissue Culture Techniques; D000077288:Troglitazone
chemical_list: D002839:Chromans; D045162:Thiazolidinediones; D012313:RNA; D000077288:Troglitazone