TNFα is persistently elevated in many injury and disease conditions. Previous reports of cytotoxicity of TNFα for oligodendrocytes and their progenitors suggest that the poor endogenous remyelination in patients with traumatic injury or multiple sclerosis may be due in part to persistent inflammation. Understanding the effects of inflammatory cytokines on potential cell therapy candidates is therefore important for evaluating the feasibility of their use. In this study, we assessed the effects of long term exposure to TNFα on viability, proliferation, migration and TNFα receptor expression of cultured rat olfactory ensheathing cells (OECs) and Schwann cells (SCs). Although OECs and SCs transplanted into the CNS produce similar myelinating phenotypes, and might be expected to have similar therapeutic uses, we report that they have very different sensitivities to TNFα. OECs exhibited positive proliferative responses to TNFα over a much broader range of concentrations than SCs. Low TNFα concentrations increased proliferation and migration of both OECs and SCs, but SC number declined in the presence of 100 ng/ml or higher concentrations of TNFα. In contrast, OECs exhibited enhanced proliferation even at high TNFα concentrations (up to 1 µg/ml) and showed no evidence of TNF cytotoxicity even at 4 weeks post-treatment. Furthermore, while both OECs and SCs expressed TNFαR1 and TNFαR2, TNFα receptor levels were downregulated in OECs after exposure to100 ng/ml TNFα for 5-7 days, but were either elevated or unchanged in SCs. These results imply that OECs may be a more suitable cell therapy candidate if transplanted into areas with persistent inflammation.

译文

tnf α 在许多损伤和疾病情况下持续升高。先前关于tnf α 对少突胶质细胞及其祖细胞的细胞毒性的报道表明,创伤性损伤或多发性硬化症患者的内源性髓鞘再生不良可能部分归因于持续的炎症。因此,了解炎性细胞因子对潜在细胞治疗候选者的影响对于评估其使用的可行性非常重要。在这项研究中,我们评估了长期暴露于tnf α 对培养的大鼠嗅鞘细胞 (OECs) 和雪旺细胞 (SCs) 的活力,增殖,迁移和tnf α 受体表达的影响。尽管移植到CNS中的OECs和SCs产生相似的髓鞘表型,并且可能具有相似的治疗用途,但我们报告它们对tnf α 的敏感性非常不同。OECs在比SCs更宽的浓度范围内对tnf α 表现出阳性增殖反应。低tnf α 浓度增加了OECs和SCs的增殖和迁移,但在100 ng/ml或更高浓度的tnf α 存在下SC数下降。相反,即使在高TNF α 浓度 (高达1 µ g/ml) 下,OECs也显示出增强的增殖,并且即使在治疗后4周也没有显示出TNF细胞毒性的证据。此外,尽管OECs和SCs均表达tnf αr1和tnf αr2,但暴露于100 ng/ml tnf α 5-7天后,OECs中的tnf α 受体水平下调,但SCs中的tnf α 受体水平升高或保持不变。这些结果表明,如果将OECs移植到具有持续炎症的区域中,则OECs可能是更合适的细胞治疗候选者。

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