Urine-derived stem cells display homing, incorporation, and regeneration in human organoid and mouse models of acute kidney injury.

Urine-derived stem cells (USCs) are adult human stem cells that can be collected noninvasively from urine and cultured in vitro. Because of their renal origin and reported therapeutic effects, we hypothesized that USCs would home to the injured kidney in acute kidney injury (AKI) models. We employed mouse models of glycerol-induced rhabdomyolysis or unilateral nephrectomy with clamping ischemia reperfusion injury to model AKI. To track USC homing by live animal imaging, we administered luciferase-expressing USCs to mice by intraperitoneal injection. We observed USC localization to both the tubules and glomeruli of injured mice within three hours by histology. We confirmed the presence of luciferase-expressing (Luc) USCs in the kidney at 3 h, 24 h, and 48 h after the injection using biodistribution analysis of quantitative bioluminescence tomography (qBLT) imaging. We performed immunostaining for kidney injury molecule-1 (KIM-1) for kidney injury and found reduced expression in USC-treated group at 24 h after injection. To evaluate the effects of the human USCs on injured human nephrons, we injured human kidney organoids with the nephrotoxin cisplatin (5 μM) followed by 5x10⁴ USCs treatment. USCs were incorporated and lowered expression of KIM-1 in the organoids. In conclusion, USCs home to injured nephrons and reduce measures of kidney injury.