Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (1): 130-136.doi: 10.4103/1673-5374.314316

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Cell cycle exit and neuronal differentiation 1-engineered embryonic neural stem cells enhance neuronal differentiation and neurobehavioral recovery after experimental traumatic brain injury

Ren Wang1, #, Dian-Xu Yang1, #, Ying-Liang Liu2, Jun Ding1, Yan Guo1, Wan-Hai Ding1, *, Heng-Li Tian1, *, Fang Yuan1, *   

  1. 1Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 2Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
  • Online:2022-01-15 Published:2021-09-18
  • Contact: Wan-Hai Ding, MD, PhD, dingwanhai@126.com; Heng-Li Tian, MD, PhD, tianhlsh@126.com; Fang Yuan, MD, PhD, yf021025@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81701895; and Shanghai Jiao Tong University Medicine-Engineering Research Fund, China, No. YG2016QN20 (both to FY).

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Abstract: Our previous study showed that cell cycle exit and neuronal differentiation 1 (CEND1) may participate in neural stem cell cycle exit and oriented differentiation. However, whether CEND1-transfected neural stem cells can improve the prognosis of traumatic brain injury remained unclear. In this study, we performed quantitative proteomic analysis and found that after traumatic brain injury, CEND1 expression was downregulated in mouse brain tissue. Three days after traumatic brain injury, we transplanted CEND1-transfected neural stem cells into the area surrounding the injury site. We found that at 5 weeks after traumatic brain injury, transplantation of CEND1-transfected neural stem cells markedly alleviated brain atrophy and greatly improved neurological function. In vivo and in vitro results indicate that CEND1 overexpression inhibited the proliferation of neural stem cells, but significantly promoted their neuronal differentiation. Additionally, CEND1 overexpression reduced protein levels of Notch1 and cyclin D1, but increased levels of p21 in CEND1-transfected neural stem cells. Treatment with CEND1-transfected neural stem cells was superior to similar treatment without CEND1 transfection. These findings suggest that transplantation of CEND1-transfected neural stem cells is a promising cell therapy for traumatic brain injury. This study was approved by the Animal Ethics Committee of the School of Biomedical Engineering of Shanghai Jiao Tong University, China (approval No. 2016034) on November 25, 2016. 

Key words: cell cycle exit and neuronal differentiation 1, cyclin D1, embryonic neural stem cells, neuronal differentiation, genetic engineering, overexpression, mice, Notch1, p21, traumatic brain injury