Mesenchymal stem cells attenuate hyperoxaluria-induced kidney injury and crystal depositions via inhibiting the activation of NLRP3 inflammasome

Abstract

Aims

Calcium oxalate (CaOx) is the predominant form of kidney stones, associated with significant morbidity and recurrence rates. Mesenchymal stem cells (MSCs) have shown promise in treating renal injury, but their impact on CaOx stone formation remains unclear.

Materials and methods

We established a hyperoxaluria-induced AKI model in mice through intraperitoneal injection of glyoxylate. Two types of MSCs, bone marrow-derived MSCs (BMSCs) and umbilical cord-derived mesenchymal stem cells (UMSCs), were injected through tail vein injection. Histological evaluations and blood biochemical tests were performed to assess crystal deposition and kidney function. The inflammatory response and NLRP3 inflammasome activation were assessed using immunofluorescence, immunohistochemistry, TUNEL staining, and qPCR. In vitro, macrophages were cocultured in the presence of MSCs. ELISA was used to measure IL-1β and IL-18 release. MTS assays assessed renal epithelial cell protection. Western blotting evaluated NLRP3 inflammasome activation in macrophages.

Key findings

Both BMSCs and UMSCs significantly inhibited CaOx crystal deposition and kidney injury by inhibiting NLRP3 inflammasome activation. In vitro, both MSC types suppressed NLRP3 inflammasome activation in macrophages through the NF-κB signaling pathway, leading to decreased release of IL-1β and IL-18 and enhanced protection of renal epithelial cells. This attenuation of renal tubular cell injury is a critical factor in preventing CaOx stone formation.

Significance

Our findings reveal that Both BMSCs and UMSCs effectively attenuate hyperoxaluria-induced kidney injury and crystal deposition by inhibiting NLRP3 inflammasome activation. This discovery is helpful for developing new effective therapeutic means for nephrolithiasis.