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Abstract: TH-OR140

Exposure to Fluid Shear Stress Enriches Tip Cell Populations in In Vitro Cultured Ureteric Bud Cells

Session Information

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Kimura, Hiroshi, Tokai University, Hiratsuka, Japan
  • Nishikawa, Masaki, GLAVAHS at Sepulveda, North Hills, California, United States
  • Yanagawa, Naomi, GLAVAHS at Sepulveda, North Hills, California, United States
  • Nakamura, Hiroko, Tokai University, Hiratsuka, Japan
  • Jo, Oak Dong, GLAVAHS at Sepulveda, North Hills, California, United States
  • Yanagawa, Norimoto, VA Greater Los Angeles Healthcare System, North Hills, California, United States
Background

Most kidney cells are exposed to fluid shear stress (FSS) from either blood flow or urine flow. Previous studies have shown that changes in FSS may affect the function or induce injury of kidney cells. However, it remains unclear whether FSS influences kidney development when urinary flow starts in the embryonic kidneys, which occurs around embryonic age E15.5 in mouse. In this study, we evaluated the influence of FSS on in vitro cultured ureteric bud (UB) cells.

Methods

We used a pumpless microfluidic device, which offers the convenience of conducting parallel cell culture experiments without the need of cumbersome electronic driven equipment. We first validated the function of the device by both mathematical model and experimental measurements. UB cells dissected from E15.5 mouse embryonic kidneys were cultured in the pumpless microfluidic device and subjected to FSS for 48 hrs. Control UB cells were similarly cultured in the device and maintained under a no-flow condition.

Results

We found that the exposure to FSS for up to 48 hrs led to an increase in mRNA expression levels of UB tip cell marker genes (Wnt11, Ret, Etv4) with a decrease in stalk cell marker genes (Wnt7b, Tacstd2). In further support of the enrichment of UB tip cell population in response to FSS, we also found that exposure to FSS led to a remarkable reduction in the binding of lectin Dolichos Biflorus Agglutinin (DBA), which is a characteristic of UB tip cells.

Conclusion

Results of our present study show that exposure to FSS led to enrichment in UB tip cell populations. Since UB tip cells are known to be the proliferative progenitor cells that contribute to the branching morphogenesis of the collecting system in the kidney, our finding could imply an important link between the FSS from the initiation of urine flow and the development of the kidney.

Funding

  • Government Support - Non-U.S.