Abstract
Reducing neuronal death after spinal cord injury (SCI) is considered to be an important strategy for the renovation of SCI. Studies have shown that, as an important regulator of the development and maintenance of neural structure, acidic fibroblast growth factor (aFGF) has the role of tissue protection and is considered to be an effective drug for the treatment of SCI. Neural stem cells (NSCs) are rendered with the remarkable characteristics to self-replace and differentiate into a variety of cells, so it is promising to be used in cell transplantation therapy. Based on the facts above, our main aim of this research is to explore the role of NSCs expressing aFGF meditated by five hypoxia-responsive elements (5HRE) in the treatment of SCI by constructing AAV–5HRE–aFGF–NSCs and transplanting it into the area of SCI. Our research results showed that AAV–5HRE–aFGF–NSCs can effectively restore the motor function of rats with SCI. This was accomplished by inhibiting the expression of caspase 12/caspase 3 pathway, EIF2α–CHOP pathway, and GRP78 protein to inhibit apoptosis.
Highlights
Spinal cord injury (SCI) is a catastrophic traumatic illness in the central nervous system (CNS), which can lead to impaired movement, sensation, and other functions (Ahuja et al, 2017; Chhabra and Sarda, 2017; Bradbury and Burnside, 2019; Song et al, 2019)
Our research shows that associated virus (AAV)–5HRE–acidic fibroblast growth factor (aFGF)–Neural stem cells (NSCs) can promote the repair of spinal cord injury (SCI) by inhibiting endoplasmic reticulum (ER) stress
In order to detect whether AAV-mediated aFGF was directly regulated by Hypoxia-response element (HRE) under hypoxia, AAV–5HRE–aFGF was structured and transduced into NSCs (Figure 1A)
Summary
Spinal cord injury (SCI) is a catastrophic traumatic illness in the central nervous system (CNS), which can lead to impaired movement, sensation, and other functions (Ahuja et al, 2017; Chhabra and Sarda, 2017; Bradbury and Burnside, 2019; Song et al, 2019). Studies have shown that the CNS is very difficult to repair, and scientists hope that advances in stem cell research may eventually restore neurocirculation in people with SCI, putting the hope of future treatment on stem cells (Bourzac, 2016). Some experiments have shown that after transplantation, most of the NSCs differentiate into corresponding cells and migrate and integrate into the host tissue due to the regulation of signal factors (DenothLippuner and Jessberger, 2021). NSCs are a good choice for stem cell transplantation in the treatment of SCI
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