Nerve Growth Factor (NGF) with Hypoxia Response Elements Loaded by Adeno-associated Virus (AAV) Combined with Neural Stem Cells Improve the Spinal Cord Injury Recovery

Overview

Journal Cell Death Discov

Date 2021 Oct 22

PMID 34675188

Citations 7

Authors

Qiuji Wu

Ziyue Xiang

Yibo Ying

Zhiyang Huang

Yurong Tu

Min Chen

Jiahui Ye

Haicheng Dou

Sunren Sheng

Xiaoyang Li

Weiyang Ying

Sipin Zhu

Affiliations

Soon will be listed here.

Abstract

The ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.

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