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Abstract: SA-PO022

A 3D Organ-on-Chip Model of the Collecting Duct for the Study of Electrolyte Disorders

Session Information

Category: Bioengineering

  • 400 Bioengineering

Authors

  • Grillo, Alessandra, University College London Research Department of Renal Medicine, London, United Kingdom
  • Zhong, Chutong, University College London Research Department of Renal Medicine, London, United Kingdom
  • Siew, Keith, University College London Research Department of Renal Medicine, London, United Kingdom
  • Walsh, Stephen B., University College London Research Department of Renal Medicine, London, United Kingdom

Group or Team Name

  • London Tubular Centre.
Background

Kidney basement membrane components play a crucial role in the function of different segments of the nephron. For example hensin is an ECM protein that promote transition between α and β intercalated cells, stimulating different mechanisms of action in the collecting duct (CD). Current models using organ-on-chip systems mainly use collagen I, without considering segment-specific compositions. Additionally, most kidney models reproduce proximal tubule systems, with no current 3D model of the collecting duct to study physiological mechanisms in vitro. Therefore, the aim of the study is to develop a 3D model of the collecting duct using organ-on-chip system by integrating more biomimetic ECM components and physiological cues.

Methods

M1-CCD cells from collecting duct were cultured on the top channel of a three-lane organ-on-chip systems (OrganoPlate, Mimetas) to produce tubular structures, where the middle channel was filled with a permeable ECM formed by collagen I. Different combinations of collagen I, collagen IV and laminin I were used as ECM scaffold. Human umbilical vein endothelial cells (HUVEC) were seeded on the bottom channel to mimic the renal vascular system in contact with the CD.

Results

M1-CCD showed intrinsic ability to form 3D structures when seeded on low-attachment plates. M1-CCD were then cultured on the OrganoPlate system including different combinations of basement membrane proteins, such as collagen IV and laminin, in addition to collagen I, to create a biomimetic environment for collecting duct epithelial cells. M1-CCD cells successfully formed a tubular structure as shown in Figure. The bottom channel was cultured with endothelial cells and transport of small ions was evaluated between the two channels.

Conclusion

We successfully developed and characterised a 3D in vitro model of the collecting duct using the organ-on-chip technology. Further steps include the incorporation of patient urine-derived epithelial and blood-derived endothelial cells to create a more accurate and personalised platform for disease modelling and drug testing.

Tubule of M1-CCD at day 6 on collagen I (Syto16 - nuclei, Phalloidin - actin filaments).

Funding

  • Other NIH Support