Interferon-γ Promotes Neuronal Repair by Transplanted Neural Stem Cells in Ischemic Rats.

Abstract

Ischemic stroke represents the leading cause of adult neurological disability, with no effective therapeutic strategy. Stem cell transplantation promises a new promising for treating stroke, through cell replacement and cytokine paracrine. However, due to the effect of hostile immune microenvironment, the survival and differentiation of stem cells are limited in vivo. Furthermore, the delayed inflammatory response to stroke induced secondary neurological injury. IFN-γ as pro-inflammatory cytokine has the potential to protect stem cell population during inflammatory response, as well as stimulates neurogenesis of stem cells. The purpose of this study was to investigate whether co-injection of neural stem cells and IFN-γ can improve therapeutic outcomes in ischemic stroke model. In this study, we found that IFN-γ did not interfere with the proliferation of neural stem cells (NSCs) in vitro and induced levels of subsequent neuronal differentiation significantly superior to those of other four cytokines BDNF, VEGF, TGF-β, and IGF-1. Co-delivery of IFN-γ (concentration: 50 ng) enhanced the effectiveness of NSC transplantation therapy in ischemic rats. And combined IFN-γ treatment significantly increased neurogenesis in vivo, with more BrdU/DCX dual-positive cells found in ischemic areas. Moreover, co-treatment with IFN-γ and NSCs exerted additional neurological benefits compared with NSC transplantation alone. In conclusion, low concentration of IFN-γ can promote the functions of transplanted NSCs and facilitate their ability of neurological repair. Thus, our findings suggest that co-delivery of NSCs and IFN-γ without genetic modification may be an effective, simple, and novel approach for the treatment of ischemic stroke.