A microfluidic renal proximal tubule with active reabsorptive function

PLoS One. 2017 Oct 11;12(10):e0184330. doi: 10.1371/journal.pone.0184330. eCollection 2017.

Abstract

In 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.

MeSH terms

  • Coculture Techniques
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Glucose / analogs & derivatives
  • Humans
  • Imaging, Three-Dimensional
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Microfluidics / methods*
  • Models, Theoretical
  • Ouabain / pharmacology
  • Renal Reabsorption* / drug effects
  • Sodium / metabolism

Substances

  • Ouabain
  • Sodium
  • Glucose