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Orbital Shear Stress Regulates Differentiation and Barrier Function of Primary Renal Tubular Epithelial Cells

Ferrell, Nicholas*; Cheng, Jin*; Miao, Simeng; Roy, Shuvo; Fissell, William H.*

doi: 10.1097/MAT.0000000000000723
Biohybrid

Primary cells cultured in vitro gradually lose features characteristic of the in vivo phenotype. Culture techniques that help maintain cell-specific phenotype are advantageous for development of tissue engineered and bioartificial organs. Here we evaluated the phenotype of primary human renal tubular epithelial cells subjected to fluid shear stress by culturing the cells on an orbital shaker. Transepithelial electrical resistance (TEER), cell density, and gene and protein expression of proximal tubule–specific functional markers were measured in cells subjected to orbital shear stress. Cells cultured on an orbital shaker had increased TEER, higher cell density, and enhanced tubular epithelial specific gene and protein expression. This is likely due at least in part to the mechanical stress applied to the apical surface of the cells although other factors including increased nutrient and oxygen delivery and improved mixing could also play a role. These results suggest that orbital shaker culture may be a simple approach to augmenting the differentiated phenotype of cultured renal epithelial cells.

From the *Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California.

Submitted for consideration February 2017; accepted for publication in revised form October 2017.

Disclosure: S. Roy and W. H. Fissell have ownership in Silicon Kidney. The other authors have no conflicts of interest to report.

Supported by National Institutes of Health (DK 092357 to N.F. and EB 021214 to S.R. and W.H.F.).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML and PDF versions of this article on the journal’s Web site (www.asaiojournal.com).

Correspondence: William H. Fissell, MD, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Ave. South, S3223 Medical Center North, Nashville, TN 37212. Email: william.fissell@vanderbilt.edu.

Copyright © 2018 by the American Society for Artificial Internal Organs