3D, human renal proximal tubule (RPTEC-TERT1) organoids 'tubuloids' for translatable evaluation of nephrotoxins in high-throughput

The importance of human cell-based in vitro tools to drug development that are robust, accurate, and predictive cannot be understated. There has been significant effort in recent years to develop such platforms, with increased interest in 3D models that can recapitulate key aspects of biology that 2D models might not be able to deliver. We describe the development of a 3D human cell-based in vitro assay for the investigation of nephrotoxicity, using RPTEC-TERT1 cells. These RPTEC-TERT1 proximal tubule organoids 'tubuloids' demonstrate marked differences in physiologically relevant morphology compared to 2D monolayer cells, increased sensitivity to nephrotoxins observable via secreted protein, and with a higher degree of similarity to native human kidney tissue. Finally, tubuloids incubated with nephrotoxins demonstrate altered Na+/K+-ATPase signal intensity, a potential avenue for a high-throughput, translatable nephrotoxicity assay.

Automated summary

Human cell-based in vitro tools are essential for drug development, and the development of robust, accurate, and predictive models is of great importance. This study presents a 3D human cell-based assay using RPTEC-TERT1 cells to investigate nephrotoxicity. The study demonstrates that the 3D "tubuloids" have distinct morphological features, increased sensitivity to nephrotoxins, and a higher degree of similarity to native human kidney tissue. The altered Na+/K+-ATPase signal intensity in tubuloids incubated with nephrotoxins also shows potential for a high-throughput, translatable nephrotoxicity assay.