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首页> 外文期刊>Molecular medicine reports >Toll-like receptor 9 agonist stimulation enables osteogenic differentiation without altering the immune status of umbilical cord mesenchymal stem cells
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Toll-like receptor 9 agonist stimulation enables osteogenic differentiation without altering the immune status of umbilical cord mesenchymal stem cells

机译:Toll样受体9激动剂刺激可促进成骨细胞分化,而不会改变脐带间充质干细胞的免疫状态

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Mesenchymal stem cells (MSCs) possess three characteristics critical to tissue regeneration; multipotency, low immunogenicity and an undifferentiated status, providing plasticity. However, increasing evidence has indicated that induction of an immune response in vivo can injure and reject MSC-based tissues. Toll-like receptors (TLRs) are a family of pathogen-associated pattern recognition receptors, which are important in bridging the innate and adaptive immune responses. TLRs have been demonstrated to exhibit important MSC biological regulatory functions in previous studies. To confirm the role of TLR9 in the immune status maintenance of MSCs isolated from umbilical cords, the present study performed assessments to detect agonist effects. Following addition of the TLR9 agonist, CpG, to an umbilical cord mesenchymal stem cell (UCMSC) culture medium, a number of methods were used to detect the changes in the biological function of the UCMSCs. Reverse transcription-quantitative polymerase chain reaction indicated increased levels of pro-inflammatory molecules and decreased expression levels of stem cell markers following exposure to the TLR9 agonist. However, flow cytometry revealed that activation of TLR9 had no effect on the proliferation of peripheral blood leukocytes or the expression of surface markers. The present study also identified that CpG-oligodeoxynucleotide promoted MSC osteogenic differentiation, while inhibiting MSC proliferation and migration. These results indicated that TLRs and their ligands may serve as regulators of MSC proliferation and differentiation, and affect the maintenance of MSC multipo-tency.
机译:间充质干细胞(MSCs)具有三个对于组织再生至关重要的特征。专能,低免疫原性和未分化状态,可塑性强。但是,越来越多的证据表明,体内免疫反应的诱导会伤害和排斥基于MSC的组织。 Toll样受体(TLR)是病原体相关模式识别受体的一个家族,在桥接先天性和适应性免疫应答中很重要。在以前的研究中已证明TLR具有重要的MSC生物学调节功能。为了确认TLR9在从脐带分离的MSC的免疫状态维持中的作用,本研究进行了评估以检测激动剂作用。将TLR9激动剂CpG添加到脐带间充质干细胞(UCMSC)培养基后,许多方法被用来检测UCMSCs生物学功能的变化。逆转录定量聚合酶链反应表明,暴露于TLR9激动剂后,促炎分子水平增加,干细胞标志物表达水平下降。但是,流式细胞仪显示TLR9的激活对外周血白细胞的增殖或表面标志物的表达没有影响。本研究还确定,CpG-寡脱氧核苷酸可促进MSC成骨分化,同时抑制MSC增殖和迁移。这些结果表明,TLR及其配体可作为MSC增殖和分化的调节剂,并影响MSC多能性的维持。

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