Urine-derived stem cells as a model for age-related kidney degeneration and chronic disease risk

Renal aging contributes to declining kidney function and heightened susceptibility to chronic kidney disease (CKD). A key factor in this process is the diminished number and functionality of renal stem/progenitor cells, though the underlying mechanisms remain incompletely understood. Human urine-derived stem/progenitor cells (USCs) represent a promising, non-invasive source with notable regenerative potential. In this study, we examined cellular proliferation, reactive oxygen species (ROS) production, and senescence-associated protein expression as indicators of age-related degeneration in renal progenitor cells. USCs obtained from older healthy and diabetic individuals were compared to those from young, healthy donors. Our results demonstrate that USCs from aged and diabetic donors exhibit significantly reduced proliferation, elevated ROS levels, and increased β-galactosidase expression. Moreover, these cells showed impaired capacity to form 3D renal spheroids with tubular-like structures over a two-week culture period, relative to young controls. Together, these findings suggest that USCs from older or diabetic individuals - when cultured in both 2D and 3D systems - serve as a valuable model for studying renal aging and progenitor cell dysfunction. This model may facilitate the identification of biomarkers for renal aging and CKD risk and inform future regenerative and therapeutic strategies.