Cell cycle exit and neuronal differentiation 1-engineered embryonic neural stem cells enhance neuronal differentiation and neurobehavioral recovery after experimental traumatic brain injury.
Cell cycle exit and neuronal differentiation 1-engineered embryonic neural stem cells enhance neuronal differentiation and neurobehavioral recovery after experimental traumatic brain injury.
复制标题
细胞周期退出和神经元分化1-工程胚胎神经干细胞增强实验性脑外伤后神经元分化和神经行为恢复
DOI：
10.4103/1673-5374.314316
复制
发表时间：
2022-01
影响因子：
6.1
通讯作者：
Yuan F
中科院分区：
文献类型：
--
作者：
Wang R;Yang DX;Liu YL;Ding J;Guo Y;Ding WH;Tian HL;Yuan F
我们前期的研究表明CEND 1基因可能参与神经干细胞的周期退出和定向分化。然而，CEND 1转染的神经干细胞是否可以改善创伤性脑损伤的预后仍不清楚。在这项研究中，我们进行了定量蛋白质组学分析，发现创伤性脑损伤后，CEND 1在小鼠脑组织中的表达下调。创伤性脑损伤后三天，我们将CEND 1转染的神经干细胞移植到损伤部位周围的区域。我们发现，在创伤性脑损伤后5周，CEND 1转染的神经干细胞移植明显减轻脑萎缩，并大大改善神经功能。体内和体外实验结果表明CEND 1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Notch1和细胞周期蛋白D1的蛋白水平，但增加CEND1转染的神经干细胞中p21的水平。用CEND 1转染的神经干细胞处理上级没有CEND 1转染的类似处理。这些发现表明，CEND 1转染的神经干细胞移植是一种有前途的创伤性脑损伤的细胞治疗。本研究于2016年11月25日获得上海交通大学生物医学工程学院动物伦理委员会批准（批件号：2016034）。
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.