Cisplatin Induces Cell Death in Rat Adult Kidney Stem/ Progenitor Cell-Derived Kidney Organoids.

Abstract

The use of stem/ progenitor cell-derived organoids to evaluate the toxicity of chemical substances has widely increased. Organoids with nephron-like structures (NLS) can be derived from rat adult kidney stem/ progenitor cells (rKS cells) using three-dimensional culture. In this study, we examined the effects of cisplatin, an anticancer drug that induces nephrotoxicity in vivo, on rKS cell-derived NLS. Twelve organoids were simultaneously derived from three-dimensionally cultured rKS cells in Matrigel matrices. The surface area of each organoid was measured using microscopy-based imaging, and the morphological changes of NLS were monitored using an image analysis method. NLS were exposed to cisplatin, and their associated effects were assessed. NLS elongated over time. The surface areas of the 12 organoids were almost constant. Cisplatin exposure induced cell death in NLS and inhibited the increase in the surface area of the organoids. Cisplatin exposure induces damage to NLS derived from rKS cells. Thus, the organoids may be valuable as an in vitro model to assess nephrotoxicity.