The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells

Biological research: BR

Yanwen Wang¹  Li Zhang¹  Li Li¹  Dan Liu²  Lei Li²  Yalun Li²  Dan Pu²  Weimin Li²  Yanqi He² 

[1] Department of Pathology, West China Hospital, Sichuan University, Cheng Du, PR China;Department of Respiratory Medicine, West China Hospital, Sichuan University, Cheng Du, PR China

关键词: Mesenchymal stem cells;    Umbilical cord;    Toll like receptor 7;    Immunogenicity;    Pro-inflammatory molecules;   

DOI  :  10.1186/0717-6287-48-6

学科分类：生物科学（综合）

来源: BioMed Central

【 摘 要 】

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.

【 授权许可】

CC BY