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.

Evaluation of the effects of extremely low frequency electromagnetic field on the levels of some inflammatory cytokines in post-stroke patients

“…Co-injection of neural stem cells and IFN-γ have been shown to improve therapeutic outcomes in a model of ischaemic stroke in rats. IFN-γ treatment significantly increased neurogenesis in vivo, and induced levels of subsequent neuronal differentiation of cytokines BDNF, VEGF, IGF-1 and TGF-β (34).…”

Neural stem cell transplantation therapy for brain ischemic stroke: Review and perspectives

“…However, IFN-γ does not hamper the ability of NSCs in vitro . Study[88] have shown that co-delivery of IFN-γ (50 ng) enhanced the effects of transplanted NSCs in ischemic rats. The study found that in the combination-treatment group, neurogenesis was significantly increased when compared to other groups in vivo .…”

“…Moreover, co-treatment with IFN-γ and NSCs provided additional beneficial neurological outcomes. Thus, low concentrations of IFN-γ can mediate NSC functions and facilitate their ability for neurological repair[88].…”

Therapeutic potential role of exosomes for ischemic stroke

“…Previous researches have shown that cell proliferation can be found in subventricular zone in rat model disposed by the middle cerebral artery occlusion (MCAO), suggesting that endogenous recovery process is started after stroke [54][55][56][57]. However, endogenous resilience may be limited due to hostile immune microenvironment over time [56,58]. In addition, the delayed inflammatory response to stroke leads to secondary neurological injury [52,58].…”

“…However, endogenous resilience may be limited due to hostile immune microenvironment over time [56,58]. In addition, the delayed inflammatory response to stroke leads to secondary neurological injury [52,58]. Insufficient endogenous stem cells after stroke can result in weak regeneration of nerve cells in the damaged area and slowdown in tissue function recovery.…”