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Abstract: PO0512

Monitoring Mitochondrial Dynamics Within a Kidney-on-Chip Platform for Investigating Disease Progression and Potential Therapeutics

Session Information

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Kann, Samuel H., Charles Stark Draper Laboratory Inc, Cambridge, Massachusetts, United States
  • Shaughnessey, Erin M., Charles Stark Draper Laboratory Inc, Cambridge, Massachusetts, United States
  • Zhang, Xin, Boston University, Boston, Massachusetts, United States
  • Vedula, Else M., Charles Stark Draper Laboratory Inc, Cambridge, Massachusetts, United States
  • Charest, Joseph L., Charles Stark Draper Laboratory Inc, Cambridge, Massachusetts, United States
Background

The kidneys rely on an abundant number of mitochondria to produce energy to drive key functions, such as fluid/electrolyte balance. Mitochondrial dysfunction has been linked to the progression of renal diseases including acute kidney injury and diabetic nephropathy. Thus, the mitochondria are a key target for therapeutic development. Kidney-on-chip platforms provide a dynamic in vivo-like tissue culture environment to investigate renal pathophysiology. Yet, it is difficult or impossible to investigate mitochondrial dynamics due to lack of real-time measurements. Here, we present a sensor integrated kidney-on-chip platform with real-time cell oxygen consumption rate (OCR) readouts for monitoring the dynamics of mitochondrial function.

Methods

Human primary renal proximal tubule epithelial cells (hRPTEC) were cultured in PREDICT96 (P96), a high-throughput organ-on-chip platform. Integrated optical- based oxygen sensors enabled measurement of dissolved oxygen. Flow was turned off to measure decreases in oxygen and compute OCR. hRPTEC were treated with mitochondrial inhibitors Oligomycin and Antimycin A and un-coupler FCCP. OCR was measured prior to and following the drug treatments.

Results

hRPTEC basal OCR was monitored under flow at 70 uL/min over a 10 day culture period. OCR decreased by 58% and 39% following treatment with Antimycin A and Oligomycin, respectively, and increased 64% following treatment with FCCP (Fig.1).

Conclusion

We demonstrated real-time and label-free monitoring of drug-induced shifts in mitochondrial respiration within a high-throughput kidney-on-chip platform. Our work enables new investigations into mitochondrial dynamics in response to nephrotoxic agents or disease progression, as well as potential therapeutics that target the mitochondria.

Figure 1: OCR shifts during drug treatment. Bars are mean ± std (N=3-4 devices). **p<0.01, ***p<0.001, one-way ANOVA.

Funding

  • Other U.S. Government Support