A microfluidic bioreactor for epithelial cell studies under fluid shear stress

Abstract

We have developed a multilayer microfluidic bioreactor to evaluate polarized epithelial cell behavior under controlled fluid shear stress. The system consists of two microfluidic chambers separated by a synthetic porous membrane which provides a substrate for cell grown and allows apical to basolateral solute transport. The system has been used to evaluate a number of shear stress‐dependent cellular behaviors in kidney epithelial cells. We found that primary human renal epithelial cells undergo cytoskeletal rearrangement when exposed to shear stress. Endocytosis, metabolism and secretion of albumin were also evaluated using the bioreactor. Fluid shear stress increased the cellular capacity for apical uptake of albumin in immortalized proximal tubule epithelial cells. Following internalization, albumin was metabolized into small molecular weight fragments and excreted into the apical and basolateral compartments. This microfluidic bioreactor is a useful tool for evaluating kidney epithelial cell behavior in response to fluid shear stress and may have broader applications for studying a variety of shear stress sensitive cell types. This work was supported by the Wildwood Foundation and a T32 training grant from the National Institutes of Health (T32‐DK‐007470–25).

Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond

“…In contrast, OoC technology can recreate FSS within its microfluidic systems, and when supplemented with ECM components, it can simulate a more realistic internal environment. Studies have shown that PTECs cultured in microfluidic devices exhibit upregulated expression of ZO-1, increased numbers of ciliated cells, and enhanced albumin uptake and degradation (Ferrell et al, 2012;Jang et al, 2013).…”