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The TLR7 agonist Imiquimod promote the immunogenicity of mesenchymal stem cells.

Zhang L, Liu D, Pu D, Wang Y, Li L, He Y, Li Y, Li L, Li W - Biol. Res. (2015)

Bottom Line: 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.We also found that the osteo-differentiation ability of UCMSCs was enhanced in the presence of Imiquimod.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.

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

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Imiquimod enhanced the expression of co-stimulatory factors and inhibted the stem cell surface markers. A: co-stimulatory molecules, B: surface markers.
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Fig2: Imiquimod enhanced the expression of co-stimulatory factors and inhibted the stem cell surface markers. A: co-stimulatory molecules, B: surface markers.

Mentions: CD80, CD86 and HLA-E were the co-stimulator molecules and played important role in immune responses. Here the flow cytometry detection showed that the expression of CD80 and CD86 were dramatically increased (48.1% and 36.1%) upon Imiquimod stimulation 72-hour compared with negative control (1.0% and 1.8%) (Figure 2A). While the expression of HLA-E showed almost no change (1.7% vs 3.1%) (Figure 2A). We then measured the expression of stem-cell marker CD29, CD59 and CD90 and found that expression of CD29 and CD90 were inhibited (86.1% and 79.8%) in the presence of Imiquimod (Figure 2B).Figure 2


The TLR7 agonist Imiquimod promote the immunogenicity of mesenchymal stem cells.

Zhang L, Liu D, Pu D, Wang Y, Li L, He Y, Li Y, Li L, Li W - Biol. Res. (2015)

Imiquimod enhanced the expression of co-stimulatory factors and inhibted the stem cell surface markers. A: co-stimulatory molecules, B: surface markers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4363195&req=5

Fig2: Imiquimod enhanced the expression of co-stimulatory factors and inhibted the stem cell surface markers. A: co-stimulatory molecules, B: surface markers.
Mentions: CD80, CD86 and HLA-E were the co-stimulator molecules and played important role in immune responses. Here the flow cytometry detection showed that the expression of CD80 and CD86 were dramatically increased (48.1% and 36.1%) upon Imiquimod stimulation 72-hour compared with negative control (1.0% and 1.8%) (Figure 2A). While the expression of HLA-E showed almost no change (1.7% vs 3.1%) (Figure 2A). We then measured the expression of stem-cell marker CD29, CD59 and CD90 and found that expression of CD29 and CD90 were inhibited (86.1% and 79.8%) in the presence of Imiquimod (Figure 2B).Figure 2

Bottom Line: 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.We also found that the osteo-differentiation ability of UCMSCs was enhanced in the presence of Imiquimod.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.

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus