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INTRODUCTION AND OBJECTIVE: To determine if the secretome from the bone marrow stem cells (BMSCs) could activate suburethral fibroblasts and accelerate simulated birth trauma-induced stress urinary incontinence (SUI) in rats.METHODS: In vitro, Cell count kit 8 (CCK8) assay, Woundhealing assay, RT-qPCR, and western blotting were performed to assess the proliferation, migration, and collagen synthesizing abilities of the suburethal fibroblasts treated with BMSC-conditioned medium (BMSC-CM). RNA-seq and PROMO database were used to screen differentially expressed genes and potential signal transduction pathway in BMSC-CM-induced fibroblasts. In vivo, SpragueeDawley (SD) rats (n[15) were divided into 3 groups and received vaginal distention (VD) þ BMSC-concentrated conditioned medium (CCM), VD þ control medium, or sham VD. Abdominal leak point pressure (LPP) and periurethral histology were observed 2 weeks after simulated birth trauma in rats.RESULTS: BMSC-CM promoted the proliferation activity, migration ability, and collagen expression of fibroblasts. Differentially expressed genes in BMSC-CM-induced fibroblasts were mainly enriched for cell adhesion, extracellular fibril organization and angiogenesis. PROMO database and western blotting suggested involving JAK2/STAT4 pathway in BMSC-CM-cultured fibroblasts. Furthermore, the JAK2 inhibitor, AG490, reversed BMSC-CM-induced activation of fibroblasts. Periurethral injection with BMSC-CCM markedly enhanced the LPP in SUI rats, which also improved collagen fibers in periurethral histology after treating BMSC-CCM.CONCLUSIONS: The BMSC secretome activates suburethral fibroblasts via JAK2/STAT4 pathway, which helps the recovery of simulated birth trauma-induced SUI in rats.

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