Modelling the effects of microgravity on the permeability of air interface respiratory epithelial cell layers |
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Authors: | Marlise A dos Santos Cynthia Bosquillon Thais Russomano Alamelu Sundaresan Felipe Falcão Christopher Marriott Ben Forbes |
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Institution: | 1. King’s College London, Pharmaceutical Science Division, 150 Stamford Street, London SE1 9NH, United Kingdom;2. Microgravity Center, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Av. Ipiranga, Prédio 30, Bloco F, Room 216, Porto Alegre, Brazil;3. Department of Biology, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA |
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Abstract: | Although it has been suggested that microgravity might affect drug absorption in vivo, drug permeability across epithelial barriers has not yet been investigated in vitro during modelled microgravity. Therefore, a cell culture/diffusion chamber was designed specifically to accommodate epithelial cell layers in a 3D-clinostat and allow epithelial permeability to be measured under microgravity conditions in vitro with minimum alteration to established cell culture techniques. Human respiratory epithelial Calu-3 cell layers were used to model the airway epithelium. Cells grown at an air interface in the diffusion chamber from day 1 or day 5 after seeding on 24-well polyester Transwell cell culture inserts developed a similar transepithelial electrical resistance (TER) to cells cultured in conventional cell culture plates. Confluent Calu-3 layers exposed to modelled microgravity in the 3D-clinostat for up to 48 h maintained their high TER. The permeability of the paracellular marker 14C-mannitol was unaffected after a 24 h rotation of the cell layers in the 3D-clinostat, but was increased 2-fold after 48 h of modelled microgravity. It was demonstrated that the culture/diffusion chamber developed is suitable for culturing epithelial cell layers and, when subjected to rotation in the 3D-clinostat, will be a valuable in vitro system in which to study the influence of microgravity on epithelial permeability and drug transport. |
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Keywords: | Drug absorption Cell culture Microgravity simulation 3D-clinostat Biological effects Permeability |
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