Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells

被引:333
作者
Blazquez, Rebeca [1 ]
Sanchez-Margallo Francisco, Miguel [1 ]
de la Rosa, Olga [2 ]
Dalemans, Wilfried [3 ]
Alvarez, Veronica [1 ]
Tarazona, Raquel [4 ]
Casado Javier, G. [1 ]
机构
[1] Minimally Invas Surg Ctr Jesus Uson, Stem Cell Therapy Unit, Ctra N-521 Km 41-8, Caceres 10071, Spain
[2] TiGenix SA, Dept Res & Dev, Madrid, Spain
[3] TiGenix NV, Tech Operat, Leuven, Belgium
[4] Univ Extremadura, Dept Physiol, Immunol Unit, Caceres, Spain
关键词
exosomes; mesenchymal stem cells; immunomodulation; lymphocytes; lymphocyte activation; DENDRITIC CELLS; STROMAL CELLS; DIFFERENTIATION; DISEASE; MICE; PROLIFERATION; INDUCTION; RESPONSES; ANTIGENS; THERAPY;
D O I
10.3389/fimmu.2014.00556
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helperT cells (activation and differentiation markers) together with functional assays (proliferation and IFN-y production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-y release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.
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页数:9
相关论文
共 47 条
[1]   Exosomes are an effective vaccine against congenital toxoplasmosis in mice [J].
Beauvillain, Celine ;
Juste, Matthieu O. ;
Dion, Sarah ;
Pierre, Josette ;
Dimier-Poisson, Isabelle .
VACCINE, 2009, 27 (11) :1750-1757
[2]   Immunosuppressive exosomes from TGF-β1 gene-modified dendritic cells attenuate Th17-mediated inflammatory autoimmune disease by inducing regulatory T cells [J].
Cai, Zhijian ;
Zhang, Wei ;
Yang, Fei ;
Yu, Lei ;
Yu, Zhou ;
Pan, JihHung ;
Wang, Lie ;
Cao, Xuetao ;
Wang, Jianli .
CELL RESEARCH, 2012, 22 (03) :607-610
[3]   NK and MSCs Crosstalk: The Sense of Immunomodulation and Their Sensitivity [J].
Casado, Javier G. ;
Tarazona, R. ;
Sanchez-Margallo, F. M. .
STEM CELL REVIEWS AND REPORTS, 2013, 9 (02) :184-189
[4]   Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells [J].
Chen, Lei ;
Zhang, Wei ;
Yue, Han ;
Han, Qin ;
Chen, Bin ;
Shi, Mingxia ;
Li, Jing ;
Li, Binzong ;
You, Shengguo ;
Shi, Yufang ;
Zhao, Robert Chunhua .
STEM CELLS AND DEVELOPMENT, 2007, 16 (05) :719-731
[5]   Relative Roles of Direct Regeneration Versus Paracrine Effects of Human Cardiosphere-Derived Cells Transplanted Into Infarcted Mice [J].
Chimenti, Isotta ;
Smith, Rachel Ruckdeschel ;
Li, Tao-Sheng ;
Gerstenblith, Gary ;
Messina, Elisa ;
Giacomello, Alessandro ;
Marban, Eduardo .
CIRCULATION RESEARCH, 2010, 106 (05) :971-U304
[6]   Human Mesenchymal Stem Cells Are Susceptible to Lysis by CD8+ T Cells and NK Cells [J].
Crop, Meindert J. ;
Korevaar, Sander S. ;
de Kuiper, Ronella ;
IJzermans, Jan N. M. ;
van Besouw, Nicole M. ;
Baan, Carla C. ;
Weimar, Willem ;
Hoogduijn, Martin J. .
CELL TRANSPLANTATION, 2011, 20 (10) :1547-1559
[7]   Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer [J].
Dai, Shengming ;
Wei, Dong ;
Wu, Zhen ;
Zhou, Xiangyang ;
Wei, Xiaomou ;
Huang, Haixin ;
Li, Guisheng .
MOLECULAR THERAPY, 2008, 16 (04) :782-790
[8]  
DelaRosa O, 2009, TISSUE ENG PT A, V15, P2795, DOI 10.1089/ten.TEA.2008.0630
[9]   Human Adipose-Derived Stem Cells Impair Natural Killer Cell Function and Exhibit Low Susceptibility to Natural Killer-Mediated Lysis [J].
DelaRosa, Olga ;
Sanchez-Correa, Beatriz ;
Morgado, Sara ;
Ramirez, Cristina ;
del Rio, Borja ;
Menta, Ramon ;
Lombardo, Eleuterio ;
Tarazona, Raquel ;
Casado, Javier G. .
STEM CELLS AND DEVELOPMENT, 2012, 21 (08) :1333-1343
[10]   Human mesenchymal stromal cells modulate T-cell responses through TNF-α-mediated activation of NF-κψB [J].
Dorronsoro, Akaitz ;
Ferrin, Izaskun ;
Manuel Salcedo, Juan ;
Jakobsson, Emma ;
Fernandez-Rueda, Jon ;
Lang, Valerie ;
Sepulveda, Pilar ;
Fechter, Karoline ;
Pennington, Dan ;
Trigueros, Cesar .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2014, 44 (02) :480-488