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Kidney Week

Abstract: TH-OR035

A High-Throughput Microfluidic Renal Proximal Tubule Model to Study CKD and CVD Risk Factors

Session Information

  • Bioengineering
    November 07, 2019 | Location: 146 A/B, Walter E. Washington Convention Center
    Abstract Time: 05:18 PM - 05:30 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Shaughnessey, Erin M., Tufts University, Medford, Massachusetts, United States
  • Haggerty, Timothy J., Draper, Cambridge, Massachusetts, United States
  • Charest, Joseph L., Draper, Cambridge, Massachusetts, United States
  • Black, Lauren D., Tufts University, Medford, Massachusetts, United States
  • Vedula, Else M., Draper, Cambridge, Massachusetts, United States
Background

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly interdependent conditions that share several risk factors, including hypertension. In the United States, hypertension affects nearly a third of CKD patients and is the second leading cause of kidney failure. However, the mechanisms contributing to the interdependency of CKD progression and hypertension are not fully understood, and platforms for studying the conditions in vitro are limited. An in vitro system capable of supporting kidney-specific function and mimicking vascular pathology in a replicable format has the potential to increase understanding of the physiological interplay and to provide a tool for drug development.

Methods

Draper has developed a high-throughput microfluidic platform, PREDICT96, that controls fluid flow to 96 independent bilayer tissue replicates. Here, we demonstrate the potential of the PREDICT96 platform for modeling renal proximal tubule responses to elevated flow rates with high fluid shear stress (5 dynes/cm2). Human renal proximal tubule epithelial cells (hRPTEC) and human microvascular endothelial cells (hMVEC) were cultured in adjacent channels under different medium perfusion rates mimicking normal and elevated blood pressure (BP) in the renal microvasculature.

Results

After 7 days, tissue was characterized based on barrier function indicated by trans-epithelial electrical resistance (TEER) and expression of proteins involved in BP regulation including luminal sodium-hydrogen exchanger 3 (NHE3) and basolateral Na+/K+–ATPase, both previously found to be upregulated in hypertension. Preliminary data shows increased RPTEC barrier function, transporter expression and cell alignment with flow-induced shear stress in the renal and microvascular channels.

Conclusion

A high-throughput in vitro model of hypertension in the renal microvasculature will have powerful implications for studying interactions between CKD and CVD and for predicting toxicity responses of human tissue.

Funding

  • Other U.S. Government Support