Urine-derived stem cells in kidney disease: progress, challenges, and future directions.

Chronic kidney disease (CKD) is a major global health burden with limited treatment options that address the underlying causes of fibrosis or promote regeneration. Urine-derived stem cells (USCs) have emerged as a promising tool in regenerative nephrology, offering a non-invasive and accessible source of multipotent cells with therapeutic potential. Sharing key properties with mesenchymal stem cells, USCs demonstrate paracrine activity, immunomodulation, and efficient extracellular vesicle (EV) production, and have shown anti-fibrotic, anti-inflammatory, and pro-regenerative effects in preclinical models of acute and chronic kidney injury. Recent advances in biomaterials and delivery technologies, including scaffold-free cell sheets and engineered EVs, have further enhanced the potential of USC-based therapies. However, challenges remain, particularly regarding functional integration, delivery optimization, and donor variability. This review summarizes the current progress in USC-based kidney therapy, identifies key limitations, and outlines future directions to support the translation of USC-based interventions into clinical practice.