Urine-derived induced pluripotent stem cells for non-invasive diagnosis of bladder cancer.

Bladder cancer (BLCA) remains one of the most prevalent and costly malignancies worldwide, largely owing to its high recurrence rate and the invasive nature of conventional surveillance modalities. Induced pluripotent stem cell (iPSC) technology offers a new framework for disease modeling and, potentially, precision diagnostics. Urine provides a non-invasive, renewable source of exfoliated urothelial and renal epithelial cells amenable to direct reprogramming. Here, we review the biological rationale, reprogramming methodology, and diagnostic potential of urine-derived iPSCs (UDiPSCs) in the context of BLCA detection and monitoring. We further discuss the genomic fidelity of UDiPSCs, the extent to which they may retain patient-relevant oncogenic features, their integration with multi-omics platforms, and the translational challenges that must be resolved before clinical deployment. Because reprogramming resets the somatic epigenome and transcriptome, we propose a tiered strategy in which methylation is assessed in parental urinary cells, genomic variants in reprogrammed clones, and transcriptional phenotypes in differentiated derivatives. Compared with urinary tumor DNA methylation panels and urine-derived tumor organoids, which currently exceed cell-based reprogramming approaches in accuracy, cost-effectiveness, and turnaround, UDiPSCs offer a distinct niche: interrogating rare, non-tumorigenic, field-altered urothelial cells that are diluted in bulk urinary DNA and do not form organoids. Collectively, UDiPSC-based platforms provide a plausible route toward non-invasive, personalized BLCA biomarkers, although clinical utility remains to be established through prospective validation.