Studying kidney physiology is essential to increase our understanding and improve the quality of life and prognosis of patients with renal diseases. Organoid cultures have been developed that enable in vitro studies of donor-specific tissue in a controlled three-dimensional (3D) environment. Organoids are 3D multicellular constructs that recapitulate structural and functional characteristics of their organ of origin. Using a modified protocol originally developed for the expansion of adult intestinal Lgr5⁺ stem cells¹, Schutgens et al. recently established kidney tubular epithelial organoids (tubuloids) derived from adult kidney tissue and urine². 

For tubuloids to more closely represent the in vivo kidney, they can be integrated into an organ-on-a-chip system, which allows flow, a more physiological tubular architecture, and interaction with vasculature or epithelial and mesenchymal cells from other organs.

Scientists at MIMETAS, Hubrecht Institute and University Medical Centre Utrecht just published a detailed protocol, led by Hans Clevers, for the establishment of tubuloid cultures from tissue and urine (1-3 weeks). The protocol describes the generation and characterization of tubuloid cell-derived three-dimensional tubular structures in a perfused microfluidic multi-chip platform (7 days). The combination of both systems yields a powerful in vitro tool that better recapitulates the complexity of the kidney tubule with donor specific properties. This should help to expand our understanding of renal physiology and disease and serve as a predictive tool for drug efficacy studies, toxicity screening and personalized medicine. In addition, the use of animal models, as well as the costs of drug development, can be reduced.

References:

1. Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009).

2. Schutgens, F. et al. Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat. Biotechnol. 37, 303–313 (2019).

Read more: 

• Kidney Proximal Tubule Model
• OrganoPlate® 3-lane 40