Toll like receptor 3 & 4 responses of human turbinate derived mesenchymal stem cells: stimulation by double stranded RNA and lipopolysaccharide.
Toll like receptor 3 & 4 responses of human turbinate derived mesenchymal stem cells: stimulation by double stranded RNA and lipopolysaccharide.
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DOI：
10.1371/journal.pone.0101558
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kim SW
中科院分区：
文献类型：
--
作者：
Hwang SH;Cho HK;Park SH;Lee W;Lee HJ;Lee DC;Oh JH;Park SH;Kim TG;Sohn HJ;Kang JM;Kim SW
多能间充质基质细胞（MSC）是治疗多种炎症或自身免疫性疾病的一种有前景的细胞疗法。在此，研究了 MSC 的 Toll 样受体 (TLR) 表达及其免疫调节作用。在本研究中，我们研究了 TLR 对人鼻甲间充质干细胞 (hTMSC) 体外培养物的免疫反应、增殖和分化潜力的影响。从废弃的下鼻甲组织中分离hTMSC后，使用FACS分析评估hTMSC中TLR2、TLR3、TLR4和TLR5等TLR的表达，并使用细胞计数试剂盒（CCK）-8评估细胞增殖。通过多重免疫分析对细胞因子和趋化因子分泌物进行 IL-1α、IL-1β、IL-4、IL-6、IL-8、IL-10、IL-12、IP-10 (CXCL10)、RANTES (CCL5)、TNF-a、GM-CSF 和 IFN-γ 分析。在成骨、软骨形成和脂肪生成介质中评估 hTMSC 的分化潜力，并通过组织学和与分化相关的基因表达进行分析。 FACS 分析显示，TLR3 和 TLR4 表达由 hTMSC 表达的表面蛋白组成，比例相对较高。 TLR4 激动剂的存在影响并显着增加 hTMSC 的增殖。特别是，hTMSC 产生一组细胞因子和趋化因子，IL-6、IL-8、IL-12、IP-10 (CXCL10)、RANTES (CCL5)、TNF-α 和 GM-CSF 的表达在 TLR4 激动剂 LPS 的作用下上调。 hTMSCs 的成骨和成脂分化潜能不受 TLR 激动剂的影响。我们得出结论，TLR4 刺激会影响 hTMSC 的 TLR 表达、增殖和免疫调节潜力。了解 TLR 对 hTMSC 影响的机制及其免疫调节特性将有助于提供一个新的靶点来改进基于干细胞的治疗策略。
Multipotent mesenchymal stromal cells (MSCs) represent a promising cell-based therapy for a number of inflammatory or autoimmune diseases. Herein, Toll like receptor (TLR) expression by MSCs and their immune regulatory roles are investigated. In this study, we investigated the influence of TLR on the immune response, proliferation, and differentiation potential of human turbinated MSC (hTMSC) cultures in vitro. After isolating hTMSCs from discarded inferior turbinate tissue, FACS analysis was used to assess the expression of TLRs such as TLR2, TLR3, TLR4, and TLR5 in hTMSCs and cell proliferation was assessed using a cell counting kit (CCK)-8. Cytokine and chemokine secretions were analyzed with multiplex immunoassays for IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IP-10 (CXCL10), RANTES (CCL5), TNF-a, GM-CSF, and IFN-γ. The differentiation potential of hTMSCs was evaluated in the osteogenic, chondogenic, and adipogeinc media and analyzed by histology and gene expression related to differentiation. FACS analysis revealed that TLR3 and TLR4 expression consisted of a relatively high percentage of the surface proteins expressed by hTMSCs. The proliferation of hTMSCs was influenced and significantly increased by the presence of TLR4 agonists. In particular, hTMSCs produced a set of cytokines and chemokines and the expression of IL-6, IL-8, IL-12, IP-10 (CXCL10), RANTES (CCL5), TNF-α, and GM-CSF were up-regulated in response to the TLR4 agonist LPS. The osteogenic and adipogeinc differentiation potential of hTMSCs was not affected by TLR agonists. We conclude that TLR4 stimulation affects TLR expression, proliferation, and the immunomodulation potential of hTMSCs. Understanding the mechanism behind TLR's influence on hTMSCs and their immunomodulating properties would be useful for providing a novel target to exploit in the improvement of stem cell-based therapeutic strategies.
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影响因子：
5.2
作者：
Tomchuck, Suzanne L.;Zwezdaryk, Kevin J.;Scandurro, Aline B.
通讯作者：
Scandurro, Aline B.
影响因子：
3.7
作者：
Hwang SH;Park SH;Choi J;Lee DC;Oh JH;Yeo UC;Kim SW;Sun DI
通讯作者：
Sun DI
影响因子：
4
作者：
Jakob, Mark;Hemeda, Hatim;Brandau, Sven
通讯作者：
Brandau, Sven
影响因子：
4.3
作者：
Raicevic, Gordana;Najar, Mehdi;Lagneaux, Laurence
通讯作者：
Lagneaux, Laurence
影响因子：
7.3
作者：
Delarosa O;Dalemans W;Lombardo E
通讯作者：
Lombardo E