The most challenging aspect of secondary progressive multiple sclerosis (SPMS) is the lack of efficient regenerative response for remyelination, which is carried out by the endogenous population of adult oligoprogenitor cells (OPCs) after proper activation. OPCs must proliferate and migrate to the lesion and then differentiate into mature oligodendrocytes. To investigate the OPC cellular component in SPMS, we developed induced pluripotent stem cells (iPSCs) from SPMS-affected donors and age-matched controls (CT). We confirmed their efficient and similar OPC differentiation capacity, although we reported SPMS-OPCs were transcriptionally distinguishable from their CT counterparts. Analysis of OPC-generated conditioned media (CM) also evinced differences in protein secretion. We further confirmed SPMS-OPC CM presented a deficient capacity to stimulate OPC in vitro migration that can be compensated by exogenous addition of specific components. Our results provide an SPMS-OPC cellular model and encouraging venues to study potential cell communication deficiencies in the progressive form of multiple sclerosis (MS) for future treatment strategies.

中文翻译：

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来自SPMS患者的iPS衍生的早期少突胶质祖细胞显示出缺乏体外细胞迁移刺激。

继发性进行性多发性硬化症（SPMS）最具挑战性的方面是缺乏有效的再生髓鞘再生反应，这是通过适当激活后的成人成年寡祖细胞（OPC）的内源性种群进行的。OPC必须增殖并迁移至病变，然后分化为成熟的少突胶质细胞。为了研究SPMS中的OPC细胞成分，我们开发了受SPMS影响的供体和年龄匹配的对照（CT）诱导的多能干细胞（iPSC）。我们证实了它们的有效和相似的OPC分化能力，尽管我们报道了SPMS-OPC在转录上与CT相对应。对OPC生成的条件培养基（CM）的分析也表明了蛋白质分泌的差异。我们进一步证实，SPMS-OPC CM表现出不足的刺激OPC体外迁移的能力，可以通过外源添加特定组分来补偿。我们的研究结果提供了SPMS-OPC细胞模型，并鼓励研究场所以逐步发展的多发性硬化症（MS）形式研究潜在的细胞通讯缺陷，以用于未来的治疗策略。