The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture
| Autor: | Alexandra Lorenz, Ilka Maschmeyer, Mathias Busek, Katharina Schimek, Roland Lauster, Uwe Marx, Eva-Maria Materne, Reyk Horland, Frank Sonntag |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2015 |
| Předmět: |
Cell physiology
skin Pathology medicine.medical_specialty vasculature toxicity test Liver cytology Biopsy General Chemical Engineering Microfluidics body-on-a-chip Biology liver Organ-on-a-chip General Biochemistry Genetics and Molecular Biology human-on-a-chip Bioreactors Tissue engineering In vivo Extracellular medicine Humans organoids Issue 98 organs-on-a-chip multi-organ chip bioengineering microphysiological systems General Immunology and Microbiology General Neuroscience Endothelial Cells Cell Differentiation Coculture Techniques Cell biology in vitro substance testing Cell culture tissue engineering Hepatic stellate cell |
| Zdroj: | Journal of Visualized Experiments : JoVE |
| ISSN: | 1940-087X |
| DOI: | 10.3791/52526-v |
| Popis: | The ever growing amount of new substances released onto the market and the limited predictability of current in vitro test systems has led to a high need for new solutions for substance testing. Many drugs that have been removed from the market due to drug-induced liver injury released their toxic potential only after several doses of chronic testing in humans. However, a controlled microenvironment is pivotal for long-term multiple dosing experiments, as even minor alterations in extracellular conditions may greatly influence the cell physiology. We focused within our research program on the generation of a microengineered bioreactor, which can be dynamically perfused by an on-chip pump and combines at least two culture spaces for multi-organ applications. This circulatory system mimics the in vivo conditions of primary cell cultures better and assures a steadier, more quantifiable extracellular relay of signals to the cells. For demonstration purposes, human liver equivalents, generated by aggregating differentiated HepaRG cells with human hepatic stellate cells in hanging drop plates, were cocultured with human skin punch biopsies for up to 28 days inside the microbioreactor. The use of cell culture inserts enables the skin to be cultured at an air-liquid interface, allowing topical substance exposure. The microbioreactor system is capable of supporting these cocultures at near physiologic fluid flow and volume-to-liquid ratios, ensuring stable and organotypic culture conditions. The possibility of long-term cultures enables the repeated exposure to substances. Furthermore, a vascularization of the microfluidic channel circuit using human dermal microvascular endothelial cells yields a physiologically more relevant vascular model. |
| Databáze: | OpenAIRE |
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