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Effect of high-BDNF microenvironment stem cells therapy on neurogenic bladder model in rats
Authors:Wen Jie Tian  Seung Hwan Jeon  Guan Qun Zhu  Eun Bi Kwon  Ga Eun Kim  Woong Jin Bae  Hyuk Jin Cho  U-Syn Ha  Sung-Hoo Hong  Ji Youl Lee  Kang Sup Kim  Sae Woong Kim
Affiliation:1.Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;2.Catholic Integrative Medicine Research Institute, the Catholic University of Korea, Seoul, Republic of Korea;3.Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China
Abstract:BackgroundThe purpose of this study is to explore the effects of high-BDNF microenvironment produced by engineered immortalized mesenchymal stem cells (imMSCs) on the neurogenic bladder (NB) and investigate underlying mechanism.MethodsMale Sprague-Dawley rat (12-week-old, weighing about 370–400 g) were purchased from a Korean company (Orient Bio Co. Seongnam, Korea) and divided into the following groups (n=32): sham control group (n=8), NB group (n=8), NB + ImMSCs group (n=8), NB + ImMSCs (BDNF) group (n=8). The major pelvic ganglion (MPG) was observed under anesthesia. Three NB groups of rats were then subjected to bilateral MPG injury. The sham control group of rats was treated with sham surgery. Cystometry were performed before the rats were sacrificed, and then MPG and bladder were collected for histochemical and Western blot analysis.ResultsMSCs treatment improves lower urinary tract function, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). MSCs treatment accelerates recovery of injured nerve tissue, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). In high BDNF environment, apoptosis was reduced more significantly and muscle tissue recovered more rapidly (P<0.01). High-BDNF microenvironment activates more BDNF/TrkB/CREB signaling pathways (P<0.01).ConclusionsIn a rat NB model caused by nerve injury, imMSCs have certain effects on nerve tissue repair. At the same time, it was proved that increasing the expression of BDNF which had specific effect on nerve injury repair could more effectively repair injured MPG in local microenvironment. The mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway and the reduction of apoptosis by highly expressed BDNF.
Keywords:Neurogenic bladder (NB)   immortalized mesenchymal stem cells   high BDNF microenvironment   upgraded BDNF engineered stem cells   BDNF/TrkB/CREB pathway
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