Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Faculty of Science, Radboud University, 6525AJ Nijmegen, The Netherlands.
NeuroDrug Research, 6525 HP Nijmegen, The Netherlands.
Cells. 2019 Sep 17;8(9):1096. doi: 10.3390/cells8091096.
Myelination of neuronal axons is essential for proper brain functioning and requires mature myelinating oligodendrocytes (myOLs). The human OL cell lines HOG and MO3.13 have been widely used as in vitro models to study OL (dys) functioning. Here we applied a number of protocols aimed at differentiating HOG and MO3.13 cells into myOLs. However, none of the differentiation protocols led to increased expression of terminal OL differentiation or myelin-sheath formation markers. Surprisingly, the applied protocols did cause changes in the expression of markers for early OLs, neurons, astrocytes and Schwann cells. Furthermore, we noticed that mRNA expression levels in HOG and MO3.13 cells may be affected by the density of the cultured cells. Finally, HOG and MO3.13 co-cultured with human neuronal SH-SY5Y cells did not show myelin formation under several pro-OL-differentiation and pro-myelinating conditions. Together, our results illustrate the difficulty of inducing maturation of HOG and MO3.13 cells into myOLs, implying that these oligodendrocytic cell lines may not represent an appropriate model to study the (dys)functioning of human (my)OLs and OL-linked disease mechanisms.
神经元轴突的髓鞘形成对于大脑的正常功能至关重要,需要成熟的髓鞘形成少突胶质细胞(myOLs)。HOG 和 MO3.13 是人少突胶质细胞系,被广泛用作研究 OL(功能障碍)的体外模型。在这里,我们应用了许多方案来诱导 HOG 和 MO3.13 细胞分化为 myOLs。然而,没有一种分化方案能导致终端 OL 分化或髓鞘形成标志物的表达增加。令人惊讶的是,所应用的方案确实导致了早期 OL、神经元、星形胶质细胞和许旺细胞标志物表达的变化。此外,我们注意到 HOG 和 MO3.13 细胞中的 mRNA 表达水平可能受到培养细胞密度的影响。最后,在几种促进 OL 分化和促进髓鞘形成的条件下,与人类神经元 SH-SY5Y 细胞共培养的 HOG 和 MO3.13 细胞并没有形成髓鞘。总之,我们的结果说明了诱导 HOG 和 MO3.13 细胞成熟为 myOLs 的困难,这意味着这些少突胶质细胞系可能不是研究人(髓鞘)OL 功能障碍和 OL 相关疾病机制的合适模型。