Overexpression of Wnt3a facilitates the proliferation and neural differentiation of neural stem cells in vitro and after transplantation into an injured rat retina.

Neural stem cell-based therapy is a promising option for repair after injury. However, poor stem cell proliferation and insufficient differentiation of the stem cells into neurons are still difficult problems. The present study investigated whether transplantation of neural stem cells (NSCs) genetically modified to express Wnt3a is a promising approach to overcome these difficulties. We explored the possibility that Wnt3a might contribute to the therapeutic effect of NSC transplantation in retinal repair. The relative promotion of proliferation and neural differentiation by modified NSCs was investigated in a rat model of optic nerve crush. A recombinant lentivirus (Lenti-Wnt3a) was engineered to express Wnt3a. NSCs infected with control lentivirus (Lenti-GFP) or Lenti-Wnt3a were transplanted into the subretinal space immediately after the optic nerve crush. The proliferation and neural differentiation activity of the NSCs were assessed in vitro and in vivo. Overexpression of Wnt3a in NSCs induced activation of Wnt signaling, promoted proliferation, and directed the differentiation of the NSCs into neurons both in vitro and in vivo. Our study suggests that Wnt3a can potentiate the therapeutic benefits of NSC-based therapy in the injured retina.