Wang Ren, Yang Dian-Xu, Liu Ying-Liang, Ding Jun, Guo Yan, Ding Wan-Hai, Tian Heng-Li, Yuan Fang
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Neural Regen Res. 2022 Jan;17(1):130-136. doi: 10.4103/1673-5374.314316.
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.
我们之前的研究表明，细胞周期退出与神经元分化因子1（CEND1）可能参与神经干细胞的周期退出和定向分化。然而，CEND1转染的神经干细胞能否改善创伤性脑损伤的预后仍不清楚。在本研究中，我们进行了定量蛋白质组学分析，发现创伤性脑损伤后，小鼠脑组织中CEND1表达下调。创伤性脑损伤三天后，我们将CEND1转染的神经干细胞移植到损伤部位周围区域。我们发现，创伤性脑损伤5周后，移植CEND1转染的神经干细胞可显著减轻脑萎缩并大大改善神经功能。体内和体外结果表明，CEND1过表达抑制神经干细胞的增殖，但显著促进其神经元分化。此外，CEND1过表达降低了CEND1转染神经干细胞中Notch1和细胞周期蛋白D1的蛋白水平，但提高了p21的水平。用CEND1转染的神经干细胞进行治疗优于未转染CEND1的类似治疗。这些发现表明，移植CEND1转染的神经干细胞是一种有前景的创伤性脑损伤细胞治疗方法。本研究于2016年11月25日获得中国上海交通大学生物医学工程学院动物伦理委员会批准（批准号：2016034）。
