The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells

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...

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Autores principales:	Zhang,Li, Liu,Dan, Pu,Dan, Wang,Yanwen, Li,Li, He,Yanqi, Li,Yalun, Li,Lei, Li,Weimin
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2015
Materias:	Mesenchymal stem cells Umbilical cord Toll like receptor 7 Immunogenicity Pro-inflammatory molecules
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100006
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spelling	oai:scielo:S0716-976020150001000062016-02-16The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cellsZhang,LiLiu,DanPu,DanWang,YanwenLi,LiHe,YanqiLi,YalunLi,LeiLi,Weimin Mesenchymal stem cells Umbilical cord Toll like receptor 7 Immunogenicity Pro-inflammatory molecules 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100006en10.1186/0717-6287-48-6
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Mesenchymal stem cells Umbilical cord Toll like receptor 7 Immunogenicity Pro-inflammatory molecules
spellingShingle	Mesenchymal stem cells Umbilical cord Toll like receptor 7 Immunogenicity Pro-inflammatory molecules Zhang,Li Liu,Dan Pu,Dan Wang,Yanwen Li,Li He,Yanqi Li,Yalun Li,Lei Li,Weimin The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells
description	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.
author	Zhang,Li Liu,Dan Pu,Dan Wang,Yanwen Li,Li He,Yanqi Li,Yalun Li,Lei Li,Weimin
author_facet	Zhang,Li Liu,Dan Pu,Dan Wang,Yanwen Li,Li He,Yanqi Li,Yalun Li,Lei Li,Weimin
author_sort	Zhang,Li
title	The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells
title_short	The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells
title_full	The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells
title_fullStr	The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells
title_full_unstemmed	The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells
title_sort	tlr7 agonist imiquimod promote the immunogenicity of msenchymal stem cells
publisher	Sociedad de Biología de Chile
publishDate	2015
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100006
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The TLR7 agonist Imiquimod promote the immunogenicity of msenchymal stem cells

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