A microfluidic renal proximal tubule with active reabsorptive function
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CitationVedula, Else M., José Luis Alonso, M. Amin Arnaout, and Joseph L. Charest. 2017. “A microfluidic renal proximal tubule with active reabsorptive function.” PLoS ONE 12 (10): e0184330. doi:10.1371/journal.pone.0184330. http://dx.doi.org/10.1371/journal.pone.0184330.
AbstractIn the kidney, the renal proximal tubule (PT) reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier. Co-culturing epithelial and endothelial cells in the microfluidic architecture enhanced viability, metabolic activity, and compactness of the epithelial layer. The resulting tissue expressed tight junctions, kidney-specific morphology, and polarized expression of kidney markers. The microfluidic PT actively performed sodium-coupled glucose transport, which could be modulated by administration of a sodium-transport inhibiting drug. The microfluidic PT reproduces human physiology at the cellular and tissue levels, and measurable tissue function which can quantify kidney pharmaceutical efficacy and toxicity.
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