Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes
| Autor: | Paul Vulto, Sebastiaan Johannes Trietsch, Jos Joore, Henriëtte L. Lanz, Arnaud Nicolas, Adrian Roth, Stefan Kustermann, Marianne K. Vormann, Karlijn Wilschut, Annie Moisan, Meily C. Setyawati, Elena Naumovska, Dorota Kurek, Thomas Hankemeier, Chee Ping Ng |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science Cell Culture Techniques General Physics and Astronomy Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences In vivo Lab-On-A-Chip Devices Extracellular Humans Barrier integrity Intestinal Mucosa Multidisciplinary Transporter General Chemistry Anatomy Microfluidic Analytical Techniques Intestinal epithelium In vitro 3. Good health Kinetics 030104 developmental biology Membrane Caco-2 Biophysics Caco-2 Cells |
| Zdroj: | Nature Communications Nature Communications, 8, 262 Nature Communications, Vol 8, Iss 1, Pp 1-8 (2017) |
| ISSN: | 2041-1723 |
| Popis: | In vitro models that better reflect in vivo epithelial barrier (patho-)physiology are urgently required to predict adverse drug effects. Here we introduce extracellular matrix-supported intestinal tubules in perfused microfluidic devices, exhibiting tissue polarization and transporter expression. Forty leak-tight tubules are cultured in parallel on a single plate and their response to pharmacological stimuli is recorded over 125 h using automated imaging techniques. A study comprising 357 gut tubes is performed, of which 93% are leak tight before exposure. EC50-time curves could be extracted that provide insight into both concentration and exposure time response. Full compatibility with standard equipment and user-friendly operation make this Organ-on-a-Chip platform readily applicable in routine laboratories. Efforts to determine the effects of drugs on epithelial barriers could benefit from better in vitro models. Here the authors develop a microfluidic device supporting the growth and function of extracellular matrix-supported intestinal tubules, and evaluate the effect of staurosporine and acetylsalicylic acid on barrier integrity. |
| Databáze: | OpenAIRE |
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