Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model.
Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury.
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio;
Kangli
K
Deng
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio;
Dan Li
DL
Lin
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio;
Brett
B
Hanzlicek
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio;
Brian
B
Balog
Department of Integrative Medical Sciences, Northeast Ohio University College of Medicine, Rootstown, Ohio; Summa Cardiovascular Institute, Summa Health System, Akron, Ohio; and.
Marc S
MS
Penn
Department of Integrative Medical Sciences, Northeast Ohio University College of Medicine, Rootstown, Ohio;
Matthew J
MJ
Kiedrowski
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
Zhiquan
Z
Hu
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
Zhangqun
Z
Ye
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio; Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
Hui
H
Zhu
Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio; Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, Ohio damasem@ccf.org.
Margot S
MS
Damaser
D000818:Animals; D017077:Culture Media, Conditioned; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D036801:Parturition; D060525:Pudendal Nerve / Q000293:injuries / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D014521:Urethra / Q000293:injuries / Q000502:physiology*; D014550:Urinary Incontinence, Stress / Q000209:etiology / Q000517:prevention & control*
D017077:Culture Media, Conditioned
elastin; external urethral sphincter; paracrine action; pudendal nerve; urinary incontinence