Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Medday Pharmaceuticals Inc., Boston, Massachusetts, United States of America.
PLoS One. 2020 May 29;15(5):e0233859. doi: 10.1371/journal.pone.0233859. eCollection 2020.
Mechanisms implicated in disease progression in multiple sclerosis include continued oligodendrocyte (OL)/myelin injury and failure of myelin repair. Underlying causes include metabolic stress with resultant energy deficiency. Biotin is a cofactor for carboxylases involved in ATP production that impact myelin production by promoting fatty acid synthesis. Here, we investigate the effects of high dose Biotin (MD1003) on the functional properties of post-natal rat derived oligodendrocyte progenitor cells (OPCs). A2B5 positive OPCs were assessed using an in vitro injury assay, culturing cells in either DFM (DMEM/F12+N1) or "stress media" (no glucose (NG)-DMEM), with Biotin added over a range from 2.5 to 250 μg/ml, and cell viability determined after 24 hrs. Biotin reduced the increase in OPC cell death in the NG condition. In nanofiber myelination assays, biotin increased the percentage of ensheathing cells, the number of ensheathed segments per cell, and length of ensheathed segments. In dispersed cell culture, Biotin also significantly increased ATP production, assessed using a Seahorse bio-analyzer. For most assays, the positive effects of Biotin were observed at the higher end of the dose-response analysis. We conclude that Biotin, in vitro, protects OL lineage cells from metabolic injury, enhances myelin-like ensheathment, and is associated with increased ATP production.
多发性硬化症疾病进展中涉及的机制包括持续的少突胶质细胞（OL）/髓鞘损伤和髓鞘修复失败。潜在的原因包括代谢应激导致能量不足。生物素是参与 ATP 产生的羧化酶的辅助因子，通过促进脂肪酸合成来影响髓鞘的产生。在这里，我们研究了高剂量生物素（MD1003）对产后大鼠来源的少突胶质前体细胞（OPC）功能特性的影响。使用体外损伤测定法评估 A2B5 阳性 OPC，将细胞在 DFM（DMEM/F12+N1）或“应激培养基”（无葡萄糖（NG）-DMEM）中培养，生物素添加范围为 2.5 至 250μg/ml，并在 24 小时后测定细胞活力。生物素减少了 NG 条件下 OPC 细胞死亡的增加。在纳米纤维髓鞘形成测定中，生物素增加了包绕细胞的百分比、每个细胞的包绕段数和包绕段的长度。在分散细胞培养中，生物素也显著增加了使用 Seahorse 生物分析仪评估的 ATP 产生。对于大多数测定，生物素的积极作用在剂量反应分析的较高端观察到。我们得出结论，生物素在体外可保护 OL 谱系细胞免受代谢损伤，增强类髓鞘包绕，并与增加的 ATP 产生相关。
