No abstract

Microphysiological systems are an emerging area of in vitro drug development, and their independent evaluation is important for wide adoption and use. The primary goal of this study was to test reproducibility and robustness of a renal proximal tubule microphysiological system, OrganoPlate® 3-lane 40, as an in vitro model for drug transport and toxicity studies. This microfluidic model was compared to static multi-well cultures and tested using several human renal proximal tubule epithelial cell (RPTEC) types. The model was characterized in terms of the functional transport for various tubule-specific proteins, epithelial permeability of small molecules (cisplatin, tenofovir and perfluorooctanoic acid) versus to large-molecules (fluorescent dextrans, 60-150 kDa), and gene expression response to a nephrotoxic xenobiotic. The advantages offered by OrganoPlate® 3-lane 40 as compared to multi-well cultures are presence of media flow, albeit intermittent, and increased throughput compared to other microfluidic models. However, OrganoPlate® 3-lane 40 model appeared to offer only limited (e.g., MRP-mediated transport) advantages in terms of either gene expression or functional transport when compared to the multi-well plate culture conditions. While OrganoPlate® 3-lane 40 can be used to study cellular uptake and direct toxic effects of small molecules, it may have limited utility for studies for drug transport studies. Overall, this study offers refined experimental protocols and comprehensive comparative data on the function of RPETCs in traditional multi-well culture and micro-fluidic OrganoPlate® 3-lane 40, information that will be invaluable for the prospective end-users of in vitro models of the human proximal tubule.