title: The role of Toll-like receptor 3 and 4 in regulating the function of mesenchymal stem cells isolated from umbilical cord.
abstract: Mesenchymal stem cells (MSCs) have been applied to cell-based therapy due to their multiple differentiation ability, the low expression of co-stimulatory molecules and immunosuppressive properties. Despite their immunomodulatory role, the issue of the survival and permanence of MSCs at the site of injury has not yet been fully resolved. Therefore, in order to improve the therapeutic potential of MSCs, it is important to study the mechanisms mediating the relative instability of MSCs in clinical trials. The Toll-like receptors (TLRs) are an important component of innate and adaptive immune responses. In this study, we demonstrate that the activation of two TLRs, namely TLR3 and TLR4, in human umbilical cord-derived MSCs (UCMSCs) induces the expression of inflammatory markers. In addition, as shown by our results, TLR3 upregulated the expression of stem cell markers, while TLR4 downregulated their expression. The upregulation in the expression of the inflammatory markers did not alter the immune status of the UCMSCs or mediate the immune attack of the MSCs by allogeneic immune cells. We found that the activation of TLR3 inhibited the differentiation of UCMSCs into osteocytes, while that of TLR4 increased this differentiation to a certain extent. Taken together, the results of this study provide a new role for TLR3 and TLR4 as regulators of the biological functions of UCMSCs.
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Pu
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yalun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4