Journal
AGING-US
Volume 13, Issue 7, Pages 10517-10534Publisher
IMPACT JOURNALS LLC
Keywords
stress urinary incontinence; bone marrow stem cells; secretome; fibroblasts; JAK2/STAT4
Categories
Funding
- National Natural Science Foundation of China [81670695]
- Zhejiang Provincial Medical and Health Technology Program projects of China [2018PY031, 2019KY101]
- Zhejiang Provincial Natural Science Foundation of China [LWY20H050001]
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The study showed that BMSC secretome can activate AVW fibroblasts, aiding in the acceleration of recovery from simulated birth trauma-induced SUI in rats.
Stress urinary incontinence (SUI) is defined as involuntary urine leakage during physical activities that increase the intra-abdominal pressure on the bladder. We studied bone marrow stem cell (BMSC) secretome-induced activation of anterior vaginal wall (AVW) fibroblasts and its ability to accelerate SUI recovery following vaginal distention (VD) in a rat model of birth trauma using BMSC-conditioned medium (BMSC-CM) and concentrated conditioned medium (CCM). BMSC-CM enhanced the proliferation, migration, and collagen synthesizing abilities of fibroblasts. Differentially expressed genes in BMSC-CM-induced fibroblasts were mainly enriched for cell adhesion, extracellular fibril organization and angiogenesis. Treatment with the JAK2 inhibitor AG490 reversed BMSC-CM-induced activation of the JAK2/STAT4 pathway. Periurethral injection with BMSC-CCM markedly enhanced the abdominal leak point pressure (LPP) in rats after VD. Histological analysis revealed increased numbers of fibroblasts, improved collagen fibers arrangement and elevated collagens content in the AVW of rats receiving BMSC-CCM. These findings suggest the BMSC secretome activates AVW fibroblasts and contributes to the functional and anatomic recovery of simulated birth trauma-induced SUI in rats.
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