1.Genetic engineering neural stem cell modified by lentivirus for repair of spinal cord injury in rats.
Xun TANG ; Pei-Qiang CAI ; Yue-Qiu LIN ; Martin OUDEGA ; Bas BLITS ; Ling XU ; Yun-Kang YANG ; Tian-Hua ZHOU
Chinese Medical Sciences Journal 2006;21(2):120-124
OBJECTIVETo explore the feasibility for therapy of spinal cord injury (SCI) by genetic engineering neural stem cell (NSC) modified by lentiviral vector.
METHODSFollowing the construction of the genetic engineering NSC modified by lentivirus to secrete both neurotrophic factor-3 (NT-3) and green fluorescence protein (GFP), hemisection of spinal cord at the level of T10 was performed in 56 adult Wistar rats that were randomly divided into 4 groups (n = 14), namely 3 therapeutic groups and 1 control group. The therapeutic groups were dealed with NSC, genetic engineering NSC, and concentrated lentiviral supernatant which carries both GFP and NT-3, respectively. Then used fluorescence microscope to detect the transgenic expression in vitro and in vivo, migration of the grafted cells in vivo, and used the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test to assess the recovery of function.
RESULTSThe transplanted cells could survive for long time in vivo and migrate for long distance. The stable transgenic expression could be detected in vivo. The hindlimb function of the injured rats in 3 therapeutic groups, especially those dealed with genetic engineering NSC, improved obviously.
CONCLUSIONIt is feasible to combine NSC with lentivirus for the repair of SCI. NSC modified by lentivirus to deliver NT-3, acting as a source of neurotrophic factors and function cell in vivo, has the potential to participate in spinal cord repair.
Animals ; Cell Line ; Embryonic Stem Cells ; transplantation ; Female ; Genetic Engineering ; methods ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; Lentivirus ; genetics ; Neurons ; transplantation ; Neurotrophin 3 ; genetics ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; therapy