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首页> 外文期刊>Fluids and Barriers of the CNS >Human ES-derived MSCs correct TNF-α-mediated alterations in a blood–brain barrier model
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Human ES-derived MSCs correct TNF-α-mediated alterations in a blood–brain barrier model

机译：人类ES来源的MSC在血脑屏障模型中纠正TNF-α介导的改变

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Immune 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. BMECs 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. Results 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. hES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS.
机译：免疫细胞向CNS的运输被认为有助于MS及其动物模型EAE的发病机理。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MSC相比，人胚胎干细胞来源的间充质干/基质细胞（hES-MSC）在减轻EAE的临床症状和神经病理学方面显示出优异的治疗功效。然而，尚未报道hES-MSC是否抑制和/或修复与EAE伴随的神经炎症相关的BBB损害。在所有实验中，将BMEC作为BBB模型培养在Transwell插入片段上。 BBB模型的破坏是由TNF-α引起的，TNF-α是一种促炎细胞因子，是急性和慢性神经炎症的标志。结果表明，hES-MSC逆转了TNF-α诱导的紧密连接蛋白，通透性，跨内皮电阻和粘附分子表达的变化，特别是当这些细胞与BMEC直接接触时。 hES-MSC和/或衍生自它们的产品可能潜在地作为修复MS中BBB紊乱的新疗法。

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