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Abstract: SA-OR11

Development of Physiologically Relevant In Vitro Model of Human Kidney Collecting Duct System Toward a Functional Kidney Replacement

Session Information

Category: Bioengineering

  • 400 Bioengineering

Authors

  • Gholizadeh, Shayan, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Gifford, Cody Charles, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Cai, Ling, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Michel Farías, Ana Karen, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Li, Yi, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Zhang, Y. Shrike, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States

Group or Team Name

  • Bonventre Lab.
Background

A significant number of patients with end-stage kidney disease face a restricted supply of kidney donors. Urgently needed alternatives are necessary due to the shortcomings of dialysis. Engineered kidney models have mainly focused on the proximal nephron, with little attention given to recapitulating the kidney collecting duct (CD) system. The collecting system refines formative urine and is vital for regulating acid-base balance, Na+ and K+ handling, and body water homeostasis. Applying microfluidic and 3D bioprinting methods to the development of kidney CD systems can potentially lead to a mature understanding of CD function in health and disease, as well as serve as an important component of functional kidney replacement.

Methods

PDMS soft lithography was employed to create a three-compartment cell culture device in which channels are separated by phase guides. These phase guides allow for in situ hydrogel formation while enabling subsequent fluidic exchange. These devices were designed to support both 2D cell culture for preliminary tests and as an enclosed system for fitting 3D-bioprinted tubes. Each channel is connected to a peristaltic pump channel, enabling shear stress in 2D or 3D culture. Ureteric bud-derived CD cells were seeded in the central channel, while the surrounding channels can be potentially used to culture stromal cells and endothelial cells to resemble the in vivo setting.

Results

Preliminary testing of the fabricated devices exhibited high cytocompatibility and the ability to withstand shear stress values up to 10 dynes/cm2 in the channels without mechanical failure or cell detachment. In situ hydrogel formation demonstrated the effectiveness of the phase guides in preventing mixture before crosslinking, while allowing fluidic transfer between the channels. The hydrogel structures within the devices showed sustained resistance to flow flows with no structural defects.

Conclusion

Our human kidney CD system can be used to model the CD in health and disease, as well as serve as a potential component for kidney functional replacement. Our initial studies involve demonstrating the functionality of this system to study human CD system physiological function in health and in models of genetic disease.

Funding

  • NIDDK Support