Abstract
BackgroundMesenchymal 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.ResultsOur 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.ConclusionTo 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.
Highlights
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
Activation of TLR7 pathway of UCMSC by Imiquimod dramatically increased the proliferation of Peripheral blood mononuclear cells (PBMCs) carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled leukocytes proliferation was widely used to detect the increased immune responses in co-culture system
We co-cultured PBMC with UCMSCs and added Imiqouid to activate TLR7 pathway, the negative controls were PBMC co-cultured with UCMSCs without Imiquimod and the PBMC stimulated with Imiquimod
Summary
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. The advantages of MSCs in clinical use were due to their isolation, low immunogenicity, immunosuppression effects, lack of ethical controversy and potential to differentiate into tissue-specific cell types [1]. Several reports indicated that engrafted MSCs could induce immune responses in vivo and cause the rejection or damage of MSCs, such as induction of memory T cell response [12], increased immunogenicity of differentiated MSCs [13], enhanced NK cell response [14] and complement response [15] These evidences indicated that MSCs could not hold immune privilege permanently in vivo and might induce immune response under specific conditions, but large of these mechanisms remained uncovered
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