BackgroundImmune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. Disruption of the blood–brain barrier (BBB) is a hallmark of these pathologies and a potential target of therapeutics. Human embryonic stem cell-derived mesenchymal stem/stromal cells (hES-MSCs) have shown superior therapeutic efficacy, compared to bone marrow-derived MSCs, in reducing clinical symptoms and neuropathology of EAE. However, it has not yet been reported whether hES-MSCs inhibit and/or repair the BBB damage associated with neuroinflammation that accompanies EAE.MethodsBMECs were cultured on Transwell inserts as a BBB model for all the experiments. Disruption of BBB models was induced by TNF-α, a pro-inflammatory cytokine that is a hallmark of acute and chronic neuroinflammation.ResultsResults indicated that hES-MSCs reversed the TNF-α-induced changes in tight junction proteins, permeability, transendothelial electrical resistance, and expression of adhesion molecules, especially when these cells were placed in direct contact with BMEC.ConclusionshES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS.

中文翻译：

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人 ES 衍生的 MSC 在血脑屏障模型中纠正 TNF-α 介导的改变

背景 免疫细胞进入 CNS 被认为有助于 MS 及其动物模型 EAE 的发病机制。血脑屏障 (BBB) 的破坏是这些病理的标志，也是治疗的潜在目标。与骨髓来源的间充质干细胞相比，人胚胎干细胞来源的间充质干/基质细胞 (hES-MSCs) 在减轻 EAE 的临床症状和神经病理学方面显示出更好的治疗效果。然而，尚未报道 hES-MSCs 是否抑制和/或修复与伴随 EAE 的神经炎症相关的 BBB 损伤。方法 在 Transwell 插入物上培养 BMECs 作为所有实验的 BBB 模型。BBB 模型的破坏是由 TNF-α 诱导的，TNF-α 是一种促炎细胞因子，是急性和慢性神经炎症的标志。