Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei 10617, Taiwan.
Cells. 2022 Mar 24;11(7):1091. doi: 10.3390/cells11071091.
Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular signatures similar to oligodendrocytes after treatment with valproic acid and exposure to the small molecules Y27632, SU9516, and forskolin (FSK). To pursue the development of a cell-free remyelination therapy in vivo, we used a cuprizone-induced demyelinated mouse model. The small molecules (Y27632, SU9516, and FSK) were directly injected into the demyelinated corpus callosum of the mouse brain. This combination of small molecules rescued the demyelination phenotype within two weeks as observed by light and electron microscopy. These results provide a foundation for exploring the development of a treatment for demyelinating diseases via regenerative medicine.
少突胶质细胞是位于中枢神经系统（CNS）中的神经胶质细胞，在神经信号传递和髓鞘神经元的神经保护中发挥重要作用。少突胶质细胞的功能障碍或丧失会导致脱髓鞘疾病，如多发性硬化症（MS）。为了治疗脱髓鞘疾病，需要开发一种促进髓鞘再生的治疗方法。在本研究中，我们建立了一种在 3 天内将人成纤维细胞转化为诱导性少突胶质样细胞（iOLC）的体外方法。经丙戊酸处理并暴露于小分子 Y27632、SU9516 和 forskolin（FSK）后，诱导细胞显示出与少突胶质细胞相似的形态和分子特征。为了在体内追求无细胞髓鞘再生治疗的发展，我们使用了 cuprizone 诱导的脱髓鞘小鼠模型。小分子（Y27632、SU9516 和 FSK）直接注射到小鼠大脑的脱髓鞘胼胝体中。这种小分子组合在两周内通过光镜和电子显微镜观察到挽救了脱髓鞘表型。这些结果为通过再生医学探索脱髓鞘疾病治疗方法的发展提供了基础。
