The main intention of this research was to provide a new approach for birth-injury induced stress urinary incontinence (SUI), focusing on bone marrow stem cell (BMSC) secretions and fibroblast contribution. With increasing acknowledgment of the potential role of BMSC secretions  in angiogenesis, tissue repair, immunomodulation, and anti-fibrotic, we hope to determine if BMSC secretions activate anterior vaginal wall fibroblasts (AVWFs), which play an important role in the progress of delivery associated SUI.

Primary fibroblasts were extracted from anterior vaginal wall tissues of patient with SUI and vaginal prolapse, and identified by immunofluorescence staining. BMSC conditioned medium (BMSC-CM), which contains all secretions of BMSC, was collected and purified after two-day culture in serum-free medium. The effects of BMSC-CM in AVWFs proliferation and migration were respectively assessed by CCK8 assay and cell-scratch test compared with fibroblast-CM and serum-free medium. Reverse transcription-quantitative polymerase chain reaction (RT-PCR) and western blot were used to detect the expression of collagen I and III and the activation of signal pathway. In vivo, 15 SD rats were divided into 3 groups and received vaginal distention (VD) + periurethral injection of BMSC-CM, VD + periurethral injection of control medium, or sham VD. Leak point pressure (LPP) and periurethral histology were observed 2 weeks later.

The cells we extracted were indeed fibroblasts which exhibited vimentin positive and α-SMA negative, rather than smooth muscle cells. BMSC-CM significantly enhanced the proliferation and migration ability of AVWFs compared to fibroblast-CM and control medium. BMSC-CM also accelerated the expression of collagen I, but not  collagen III at both mRNA and protein level. Western blot showed that p-STAT3, p-AKT and p-mTOR expressed at a higher level under the administration of BMSC-CM. LPP was obviously decreased in rats treated with VD + control medium compared to sham VD but not in those treated with VD + BMSC-CM. HE and Masson staining suggested that rats received VD + BMSC-CM had an improvement of collagen fiber arrangement more similar to sham VD group than rats received VD + control medium.

BMSC secretions (a combination of growth factors, cytokines and chemokines) successfully promote activation of anterior vaginal wall fibroblasts, which may contribute to functional and anatomic recovery of birth-injury caused stress incontinence simulated by vaginal distention.

In conclusion, MSC secretions facilitate recovery from SUI after simulated childbirth injury, likely via activating vaginal wall fibroblasts. BMSC secretions hold promise as a novel, noninvasive therapeutic approach for treating SUI and remain further research.