The TLR7 agonist Imiquimod promote the immunogenicity of mesenchymal stem cells.
The TLR7 agonist Imiquimod promote the immunogenicity of mesenchymal stem cells.
复制标题
TLR7激动剂咪喹莫特促进间充质干细胞的免疫原性
DOI：
10.1186/0717-6287-48-6
复制
发表时间：
2015-01-17
影响因子：
6.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Zhang L;Liu D;Pu D;Wang Y;Li L;He Y;Li Y;Li L;Li W
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）具有多向分化潜能、低表达共刺激分子（CD 80、CD 86、CD 34和HLA-II）和体内免疫抑制作用，被认为是干细胞治疗的最佳候选细胞。骨髓间充质干细胞目前已广泛应用于临床试验，但效果并不理想。主要问题是移植的MSC在体内的命运无法确定。有研究表明，骨髓间充质干细胞可诱导免疫反应，导致骨髓间充质干细胞损伤和排斥反应。由于Toll样受体（TLR）在诱导免疫应答中起重要作用，本研究探讨了TLR 7在介导脐带间充质干细胞免疫状态中的作用。我们的结果表明，TLR 7激动剂咪喹莫特可以增加从健康人志愿者中分离的PBMC的增殖和PBMC-UCMSCs共培养系统的上清液中的乳酸脱氢酶（LDH）的释放。流式细胞术和定量PCR也证实了表面共刺激分子和促炎基因（IL-6、IL-8、IL-12、TGF-β和TNF-α）的调节表达。干细胞标志物表达下调也证实了UCMSCs的干细胞性丧失。我们还发现，在咪喹莫特的存在下，UCMSCs的骨分化能力增强。据我们所知，这是首次报道TLR 7通路的激活增加了UCMSCs的免疫原性。基于骨髓间充质干细胞的亲瘤性，免疫状态的改变是否有助于肿瘤排斥反应的研究已得到广泛的研究。
Mesenchymal stem cells (MSCs) are considered the best candidate in stem cells therapy due to their multipotent differentiation ability, low expression of co-stimulatory molecules (CD80, CD86, CD34 and HLA-II) and immunosuppression effects on in vivo immune responses. MSCs were now widely used in clinical trials but received no encourage results. The major problem was the fate of engrafted MSCs in vivo could not be defined. Some studies indicated that MSCs could induce immune response and result in the damage and rejection of MSCs. As toll like receptors (TLRs) are important in inducing of immune responses, in this study we study the role of TLR7 in mediating the immune status of MSCs isolated from umbilical cord. Our results indicated that TLR7 agonist Imiquimod could increase the proliferation of PBMC isolated from healthy human volunteers and release of lactate dehydrogenase (LDH) in supernatant from PBMC-UCMSCs co-culture system. Flow cytometry and quantitative PCR also confirmed the regulated expression of surface co-stimulatory molecules and pro-inflammatory genes (IL-6, IL-8, IL-12, TGF-β and TNF-α). And the down-regulation expression of stem cell markers also confirmed the loss of stemness of UCMSCs. We also found that the osteo-differentiation ability of UCMSCs was enhanced in the presence of Imiquimod. To our knowledge, this is the first report that activation of TLR7 pathway increases the immunogenicity of UCMSCs. Extensive researches have now been conducted to study whether the change of immune status will be help in tumor rejection based on the tumor-tropism of MSCs.
登录
查看更多内容
影响因子：
13.6
作者：
Ankrum J;Karp JM
通讯作者：
Karp JM
影响因子：
20.3
作者：
Lee, OK;Kuo, TK;Chen, TH
通讯作者：
Chen, TH
Toll 样受体对成体间充质干细胞活性的调节：对治疗潜力的影响。
影响因子：
4.6
作者：
DelaRosa, Olga;Lombardo, Eleuterio
通讯作者：
Lombardo, Eleuterio
影响因子：
5.4
作者：
Chen, Guan-Yu;Shiah, Hsiao-Chiao;Hu, Yu-Chen
通讯作者：
Hu, Yu-Chen
影响因子：
4.6
作者：
Shi, M.;Liu, Z-W.;Wang, F-S.
通讯作者：
Wang, F-S.