Wang Lei, Jiang Miao, Duan Da, Zhao Zhenyu, Ge Lite, Teng Xiaohua, Liu Bo, Liu Bin, Chen Ping, Lu Ming
1 Department of Neurosurgery, the Second Affiliated Hospital of Hunan Normal University (PLA 163 Hospital), Changsha, People's Republic of China. 2 Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha, People's Republic of China. 3 Address correspondence to: Ming Lu, M.D., Department of Neurosurgery, the Second Affiliated Hospital of Hunan Normal University (PLA 163 Hospital), Changsha 410003, People's Republic of China; Ping Chen, Ph.D., Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha 410081, P.R. China.
Transplantation. 2014 Jun 27;97(12):1225-32. doi: 10.1097/TP.0000000000000118.
Recent studies provide solid evidence for the importance to delineate the combined transplantation of neural stem cells (NSCs) and olfactory ensheathing cells (OECs) for the repair of central nervous system injury. One of the limitations of this approach is that the proportion of neurons differentiated from NSCs still remains at low level. Thus, how to induce NSCs to differentiate into neurons more efficiently by OECs is an attractive problem, which needs attention to be resolved. In the present study, we investigated the effects of hyperthermia-conditioned OEC-conditioned medium (OCM) on induction of NSCs into nerve cells.
The conditioned medium, named 37OCM, 40OCM, and 40OCM+R (treated with HIF-1a inhibitor), were collected after OECs had been incubated at 37°C or 40°C for 6 hr, followed by incubation at 37°C for 42 hr; then, these conditioned medium were collected and used for NSC induction.
Results of the present study demonstrated for the first time that 6 hr of hyperthermia (40°C) could induce OECs upregulation and the expression of hypoxia-inducible factor-1 alpha (HIF-1α). Moreover, compared with 37OCM and 40OCM+R, 40OCM could induce NSCs differentiation into neurons more efficiently, and this phenomenon is associated with the upregulation of HIF-1α after hyperthermia conditioning.
The data implied that the secretory protein in OECs-cultured medium and upregulation of HIF-1α expression and binding activity induced by hyperthermia-conditioned OECs have synergistic effect to induce NSCs differentiation into a neural lineage.
最近的研究为阐明神经干细胞（NSCs）和嗅鞘细胞（OECs）联合移植对中枢神经系统损伤修复的重要性提供了确凿证据。这种方法的局限性之一是，从神经干细胞分化而来的神经元比例仍然很低。因此，如何通过嗅鞘细胞更有效地诱导神经干细胞分化为神经元是一个引人关注的问题，需要加以解决。在本研究中，我们研究了热应激条件下的嗅鞘细胞条件培养基（OCM）对神经干细胞向神经细胞诱导分化的影响。
将嗅鞘细胞在37°C或40°C孵育6小时，然后在37°C孵育42小时后收集条件培养基，分别命名为37OCM、40OCM和40OCM+R（用HIF-1α抑制剂处理）；然后，收集这些条件培养基并用于神经干细胞诱导。
本研究结果首次表明，6小时的热应激（40°C）可诱导嗅鞘细胞上调并表达缺氧诱导因子-1α（HIF-1α）。此外，与37OCM和40OCM+R相比，40OCM能更有效地诱导神经干细胞分化为神经元，且这种现象与热应激条件下HIF-1α的上调有关。
数据表明，嗅鞘细胞培养基中的分泌蛋白以及热应激条件下的嗅鞘细胞诱导的HIF-1α表达上调和结合活性对诱导神经干细胞分化为神经谱系具有协同作用。
