<p>Raw data-PCR.</p>

Introduction Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising approach to enhance remyelination; however, the influence of the OPCs’ microenvironmental origin on their therapeutic efficacy remains unclear. This study compared the remyelinating capacity of OPCs isolated from inflammatory (lipopolysaccharide) and non-inflammatory (cuprizone) microenvironments after transplanting into the corpus callosum and examined their effects on extracellular matrix chondroitin sulfate proteoglycans (CSPGs). Methods OPCs were isolated from two microenvironments and characterized by immunocytochemistry and RT-qPCR. After transplanting, OPC homing, remyelination, gene expression, and CSPG levels were evaluated using DiI labeling, LFB staining, RT-qPCR, and immunofluorescence, respectively. Results Severe demyelination exhibited in the cuprizone group compared with healthy controls (p < 0.001) by Luxol fast blue staining. Myelin content significantly increased in both transplating OPCs groups (p < 0.001), with a higher impact observed in mice received OPCs isolated from cuprizone as compared with lipopolysaccharide (p < 0.001). Also, RT-qPCR analysis exhibited significantly reduced MBP expression in the cuprizone group, whereas was significantly increased after OPC transplantation, particularly in the cuprizone-derived OPC group (p < 0.001), whereas a lower increased with lipopolysaccharide-derived OPCs (p < 0.01). MOG expression exhibited a same pattern, with a significantly increase in the cuprizone-derived OPC group compared with both the cuprizone and lipopolysaccharide-derived OPC groups (p < 0.001). Additionally, Immunofluorescence analysis exhibited increasing CSPG4 levels in the cuprizone group, but significantly reduced after OPC transplantation (p < 0.001). Notably, in the cuprizone-derived OPC group higher reduction of CSPG4 levels observed compare with in the lipopolysaccharide-derived OPC group (p < 0.001). Conclusion OPC transplantation improves remyelination and reduces the CSPG level, but the effectiveness is more related to the previous history of the OPC isolation microenvironment and the new donor.引言 多发性硬化（Multiple sclerosis）是一种中枢神经系统慢性脱髓鞘疾病。少突胶质细胞祖细胞（oligodendrocyte progenitor cells, OPCs）移植是促进髓鞘再生的极具潜力的治疗手段，但OPCs的微环境起源对其治疗效果的影响仍不明确。本研究比较了从炎性（脂多糖，lipopolysaccharide）与非炎性（铜嗪，cuprizone）微环境中分离的OPCs移植至胼胝体（corpus callosum）后的髓鞘再生能力，并检测了其对细胞外基质硫酸软骨素蛋白聚糖（extracellular matrix chondroitin sulfate proteoglycans, CSPGs）的影响。 方法 本研究从两种微环境中分离OPCs，并通过免疫细胞化学（immunocytochemistry）与实时定量聚合酶链式反应（RT-qPCR）对其进行鉴定。移植后，分别采用DiI标记（DiI labeling）、卢卡斯坚牢蓝（Luxol fast blue, LFB）染色、RT-qPCR与免疫荧光（immunofluorescence）检测OPCs的归巢能力、髓鞘再生情况、基因表达水平以及CSPGs的表达水平。 结果 卢卡斯坚牢蓝染色结果显示，与健康对照组相比，铜嗪组出现严重脱髓鞘病变（p < 0.001）。两组OPC移植小鼠的髓鞘含量均显著升高（p < 0.001），其中接受铜嗪来源OPCs移植的小鼠髓鞘修复效果优于脂多糖来源OPCs移植组（p < 0.001）。RT-qPCR分析显示，铜嗪组的髓鞘碱性蛋白（MBP）表达水平显著降低，而OPC移植后其表达显著升高，其中铜嗪来源OPCs移植组升高更为显著（p < 0.001），脂多糖来源OPCs移植组升高幅度相对较低（p < 0.01）。髓鞘少突胶质细胞糖蛋白（MOG）的表达模式与MBP一致，铜嗪来源OPCs移植组的MOG表达水平显著高于铜嗪组与脂多糖来源OPCs移植组（p < 0.001）。此外，免疫荧光分析显示，铜嗪组的CSPG4表达水平升高，而OPC移植后其表达显著降低（p < 0.001）；值得注意的是，铜嗪来源OPCs移植组的CSPG4水平降低幅度显著高于脂多糖来源OPCs移植组（p < 0.001）。 结论 OPC移植可促进髓鞘再生并降低CSPGs水平，但其治疗效果更与OPCs分离时所处的微环境背景及移植受体的微环境密切相关。