There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1 + ) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1-). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1 + , imMSCs/eSDF-1 - , or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1 + expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1 + improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1 + group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1 + group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1 + group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.
Cell transplantation. 0000 Jan [Epub]
Guan Qun Zhu, Seung Hwan Jeon, Kyu Won Lee, Hyuk Jin Cho, U-Syn Ha, Sung-Hoo Hong, Ji Youl Lee, Eun Bi Kwon, Hyo-Jin Kim, Soon Min Lee, Hey-Yon Kim, Sea Woong Kim, Woong Jin Bae
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Department of Stem Cell Therapy, SL BIGEN, Seongnam, Republic of Korea.