Title : Granulocyte Colony Stimulating Factor (G-CSF) gene therapy as a regenerative treatment strategy in BCAO stroke mouse model
Abstract:
Ischemic stroke is one of the leading causes of death and long-term disability worldwide. While tissue plasminogen activator (t-PA) is a primary clinical treatment in Emergency care, its efficacy is limited to a narrow therapeutic window, which is less than 4.5 hours post-onset. Thus, novel therapeutic strategies that protect the remaining brain tissue past the limited time-window period and promote neural regeneration are urgently required. The human Granulocyte Colony Stimulating Factor (G-CSF) gene therapy is a promising candidate for treatment in ischemic stroke because of its dual role: in both Neuroprotection and Neuroregeneration.
Our laboratory previously demonstrated that the human G-CSF gene therapy reduces mitochondrial and endoplasmic reticulum stress in a mouse model of global ischemia induced by Bilateral Carotid Artery Occlusion (BCAO). The current study investigates its regenerative potential for endogenous repair through promoting neurogenesis. Our findings show that G-CSF gene therapy enhanced proliferation and differentiation of neural stem cells and progenitor cells within neurogenic niche of Subgranular zone (SGZ) of dentate gyrus and Subventricular zone (SVZ). At 7 days post-BCAO, the treatment increased the numbers of quiescent stem cells, proliferating neural stem cells, progenitor cells, and immature neurons that were observed within these regions. In addition, human G-CSF gene therapy may also support the newly formed neurons by promoting Oligodendrogenesis, which is a mainstay for myelin synthesis and repair. Furthermore, at more prolonged time-points of 14 days and 28 days an increase was found in immature and mature neuronal populations in the treatment group which indicates the sustained regenerative effects of the drug
