Effects of transplantation of Ang-1 gene modified bone marrow mesenchymal stem cells on behavior of cerebral infarction rats

LIU Kai; JIANG Yun-xia; DENG Wen-shuai; HOU Chang-jiang; YU Cheng; SUN Peng

doi:10.3969/j.issn.1002-266X.2015.40.002

Abstract：Objective To investigate the effects of adenovirus-mediated angiopoietin-1 ( Ang-1 ) gene modified bone marrow mesenchymal stem cells ( MSCs) transplantation on the behavior of the cerebral infarction rats in order to provide the basis for clinical application.Methods MSCs were isolated and cultured in vitro, and infected by the recombinant ad-enovirus vectors carrying Ang-1 gene ( Ang-MSCs cells) or the empty adenovirus ( Null-MSCs cells) .Adult male rats were subjected to transient (2 h) middle cerebral artery occlusion ( MCAO) with modified Zea Longa method.The rat models were randomly divided into four groups (n=6): sham operation group, saline group, Null-MSCs group and Ang-MSCs group.The saline, Null-MSCs and Ang-MSCs groups were respectively transplanted with 1 mL of saline, Null-MSCs cells (5.0 ×109 cell/mL) and Ang-MSCs cells (5.0 ×109 cell/mL) into the tail vein of rats at 24 h after MCAO.The middle cerebral artery was not blocked in the sham operation group, but they were trsnsplanted with 1 mL of saline into the tail vein of rats at the same time.Morris Water Maze was used to detect the spatial learning and memory abilities of rats at 1 week post-transplantation.Results Western blotting indicated that Ang-MSCs stably expressed Ang-1 protein.One week later, compared with the sham operation group, the escape latency of Water Maze was significantly lengthened and the times of crossing the original table in 2 minutes were decreased (P<0.05 or P<0.01) in the saline, Null-MSCs and Ang-MSCs groups.Compared with the saline group, the escape latency of Water Maze was significantly shortened (all P<0.01) and the times of crossing the original table in 2 minutes were significantly increased (all P<0.01) in the Null-MSCs and Ang-MSCs groups, and the Ang-MSCs group showed the most significant improvement (P<0.05 or P<0.01).Conclusion Ang-1 gene modified MSCs can improve the spatial learning and memory abilities of the cerebral infarction rats.