Human Urine-derived Stem Cells Improve Bladder Function After Partial Bladder Outlet Obstruction: Preliminary Data and the microRNA–mRNA Expression Profile of Bladder Tissue

Abstract Background: Partial bladder outlet obstruction (pBOO), a common urological disease, often results in bladder tissue inflammation and tissue remodeling. Human urine-derived stem cells (hUSCs) have shown therapeutic benefits in various organ injury models. We used a rat model to investigate the effect of hUSCs on bladder function in pBOO rats and explore the miRNA and gene expression profiles in bladder tissue using RNA-sequencing.Methods: In total, 18 rats were randomly and evenly assigned to three groups: a sham surgery group, a pBOO without USCs therapy group, and a pBOO with USCs therapy group (treated with hUSCs six times every other week). All rats were subjected to routine urodynamic monitoring. Detrusor muscle strips were evaluated and pathophysiology was assessed. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA-sequencing and bioinformatic analysis technology.Results: After USC treatment, urodynamic monitoring revealed elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor contractility and carbachol sensitivity in pBOO rats. Histology and TUNEL assay showed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs in pBOO rats was reversed by USC treatment. Bioinformatic analysis identified miR-142 and miR-9a as the two largest nodes of differentially expressed miRNAs in the miRNA‑gene interaction network. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions.Conclusions: This is the first study to reveal the protective effect of hUSCs on bladder function and bladder remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects have not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction related pathways may be involved.