Culture and analysis of kidney tubuloids and perfused tubuloid cells-on-a-chip

Nat Protoc. 2021 Apr;16(4):2023-2050. doi: 10.1038/s41596-020-00479-w. Epub 2021 Mar 5.

Abstract

Advanced in vitro kidney models are of great importance to the study of renal physiology and disease. Kidney tubuloids can be established from primary cells derived from adult kidney tissue or urine. Tubuloids are three-dimensional multicellular structures that recapitulate tubular function and have been used to study infectious, malignant, metabolic, and genetic diseases. For tubuloids to more closely represent the in vivo kidney, they can be integrated into an organ-on-a-chip system that has a more physiological tubular architecture and allows flow and interaction with vasculature or epithelial and mesenchymal cells from other organs. Here, we describe a detailed protocol for establishing tubuloid cultures from tissue and urine (1-3 weeks), as well as for generating and characterizing tubuloid cell-derived three-dimensional tubular structures in a perfused microfluidic multi-chip platform (7 d). The combination of the two systems yields a powerful in vitro tool that better recapitulates the complexity of the kidney tubule with donor-specific properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Fractionation
  • Child
  • Child, Preschool
  • Electric Impedance
  • Female
  • Fluorescent Dyes / chemistry
  • Humans
  • Infant
  • Kidney Tubules / growth & development*
  • Lab-On-A-Chip Devices*
  • Male
  • Membrane Transport Proteins / metabolism
  • Microfluidics
  • Middle Aged
  • Organoids / growth & development*
  • Perfusion*
  • Rats
  • Tissue Culture Techniques / methods*
  • Young Adult

Substances

  • Fluorescent Dyes
  • Membrane Transport Proteins