Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries
机构：[1]Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States,[2]Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, United States,[3]Department of Urology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China,华中科技大学同济医学院附属同济医院[4]Department of Biology, University of Akron, Akron, OH, United States,[5]Department of Urology, Xuanwu Hospital, Capital Medical University, Beijing, China,外科系统泌尿外科首都医科大学宣武医院[6]Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, United States
Traumatic neuromuscular injury to the pudendal nerve and urethra during childbirth does not regenerate well and contributes to stress urinary incontinence in women. Mesenchymal stem cells (MSCs) can improve neuroregeneration via their secretions, or secretome, which includes brain-derived neurotrophic factor (BDNF). In this study, we investigated whether BDNF is a key factor in the secretome of MSCs for the facilitation of functional recovery following a dual simulated childbirth injury. BDNF knockdown (KD) MSCs were created using an anti-BDNF shRNA lentivirus vector. A scrambled sequence was used as a transduction control (scrambled). Cells were cultured for 24 h before media was concentrated 50x to create concentrated conditioned media (CCM) containing MSC secretome. CCM of unmanipulated MSCs was screened for high BDNF expression (high BDNF CCM). Concentrated control media (CM) was created by concentrating media not conditioned by cells. Female Sprague-Dawley rats underwent bilateral pudendal nerve crush and vaginal distension (Injury) or sham injury. One hour and 1 week after injury, sham injured rats received CM, and injured rats received CM, high BDNF CCM, KD CCM, or scrambled CCM (300 mu l intraperitoneally). Three weeks after injury, rats underwent leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings. The urethra and pudendal nerve were harvested for anatomical assessment. ANOVA followed by the Student-Newman-Keuls test determined significant differences between groups (p < 0.05). BDNF KD CCM had significantly decreased BDNF concentration compared to scrambled CCM, while the concentration in high BDNF CCM was significantly increased. LPP was significantly decreased in CM and KD CCM treated animals compared to sham injury, but not with scrambled or high BDNF CCM. PNSBP firing rate showed a significant decrease with CM treatment compared to sham injury. Neuromuscular junctions in the urethral sphincter in KD CCM, scrambled CCM, and high BDNF CCM were healthier than CM treated rats. While anatomical and nerve function tests demonstrate regeneration of the pudendal nerve with any CCM treatment, LPP results suggest it takes longer to recover continence with reduced BDNF in CCM. BDNF in MSC CCM is an important factor for the acceleration of recovery from a dual nerve and muscle injury.
基金：
This project was supported in part by Dept. of Veterans
Affairs RR&D Merit Review A1262R and 1 IK6 RX003843,
VA Senior Research Career Scientist Award to MD. This
project was also supported in part by Cleveland Clinic Lerner
Research Institute.
第一作者机构：[1]Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States,[2]Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, United States,[3]Department of Urology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States,[2]Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, United States,[6]Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, United States
推荐引用方式(GB/T 7714)：
Yuan Xiaoyi,Balog Brian M.,Lin Dan Li,et al.Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries[J].FRONTIERS IN CELLULAR NEUROSCIENCE.2022,16:doi:10.3389/fncel.2022.866094.
APA：
Yuan, Xiaoyi,Balog, Brian M.,Lin, Dan Li,Hanzlicek, Brett,Kuang, Mei...&Damaser, Margot S..(2022).Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries.FRONTIERS IN CELLULAR NEUROSCIENCE,16,
MLA：
Yuan, Xiaoyi,et al."Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries".FRONTIERS IN CELLULAR NEUROSCIENCE 16.(2022)
