title: Rat mesenchymal stem cell secretome promotes elastogenesis and facilitates recovery from simulated childbirth injury.
abstract: Vaginal delivery is a risk factor for stress urinary incontinence (SUI). Mesenchymal stem cells (MSCs) home to injured organs and can facilitate repair. The goal of this study was to determine if MSCs home to pelvic organs after simulated childbirth injury and facilitate recovery from SUI via paracrine factors. Three experiments were performed. Eighteen female rats received vaginal distension (VD) or sham VD and labeled intravenous (IV) MSCs to investigate if MSCs home to the pelvic organs. Whole-organ imaging and immunofluorescence were performed 1 week later. Thirty-four female rats received VD and IV MSCs, VD and IV saline, or sham VD and IV saline to investigate if MSCs accelerate recovery of continence. Twenty-nine female rats received VD and periurethral concentrated conditioned media (CCM), VD and periurethral control media, or sham VD and periurethral control media to investigate if factors secreted by MSCs accelerate recovery from VD. Urethral histology and function were assessed 1 week later. Significantly more MSCs were observed in the urethra, vagina, and spleen after VD compared to sham VD. Continence as measured by leak point pressure (LPP) was significantly reduced after VD in rats treated with saline or control media compared to sham VD but not in those given MSCs or CCM. External urethral sphincter (EUS) function as measured by electromyography (EMG) was not improved with MSCs or CCM. Rats treated with MSCs or CCM demonstrated an increase in elastin fibers near the EUS and urethral smooth muscle more similar to that of sham-injured animals than rats treated with saline or control media. MSCs homed to the urethra and vagina and facilitated recovery of continence most likely via secretion of paracrine factors. Both MSCs and CCM have promise as novel noninvasive therapies for SUI.
authors.affiliation: Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Charuspong
authors.initials: C
authors.lastname: Dissaranan
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Cruz
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kiedrowski
authors.forename: Brian M
authors.initials: BM
authors.lastname: Balog
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Gill
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
authors.forename: Howard B
authors.initials: HB
authors.lastname: Goldman
authors.forename: Margot S
authors.initials: MS
authors.lastname: Damaser
mesh_terms: D000818:Animals; D036861:Delivery, Obstetric / Q000009:adverse effects; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D036801:Parturition; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014550:Urinary Incontinence, Stress / Q000209:etiology / Q000628:therapy*; D014621:Vagina / Q000293:injuries* / Q000473:pathology