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.
引用
收藏
页数:9
相关论文
共 47 条
[11]   Interaction Between Adipose Tissue-Derived Mesenchymal Stem Cells and Regulatory T-Cells [J].
Engela, Anja U. ;
Baan, Carla C. ;
Peeters, Annemiek M. A. ;
Weimar, Willem ;
Hoogduijn, Martin J. .
CELL TRANSPLANTATION, 2013, 22 (01) :41-54
[12]   On the interactions between mesenchymal stem cells and regulatory T cells for immunomoculation in transplantation [J].
Engela, Anja U. ;
Baan, Carla C. ;
Dor, Frank J. M. F. ;
Weimar, Willem ;
Hoogduijn, Martin J. .
FRONTIERS IN IMMUNOLOGY, 2012, 3
[13]   Immunomodulatory effect of mesenchymal stem cells on B cells [J].
Franquesa, Marcella ;
Hoogduijn, M. J. ;
Bestard, O. ;
Grinyo, J. M. .
FRONTIERS IN IMMUNOLOGY, 2012, 3
[14]   Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines [J].
Geginat, J ;
Lanzavecchia, A ;
Sallusto, F .
BLOOD, 2003, 101 (11) :4260-4266
[15]   Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities [J].
Hoogduijn, M. J. ;
Crop, M. J. ;
Peeters, A. M. A. ;
van Osch, G. J. V. M. ;
Balk, A. H. M. M. ;
Ijzermans, J. N. M. ;
Weimar, W. ;
Baan, C. C. .
STEM CELLS AND DEVELOPMENT, 2007, 16 (04) :597-604
[16]   MICROENCAPSULATION TECHNOLOGY BY NATURE: CELL DERIVED EXTRACELLULAR VESICLES WITH THERAPEUTIC POTENTIAL [J].
Kittel, A. ;
Falus, A. ;
Buzas, E. .
EUROPEAN JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY, 2013, 3 (02) :91-96
[17]   MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease [J].
Kordelas, L. ;
Rebmann, V. ;
Ludwig, A-K ;
Radtke, S. ;
Ruesing, J. ;
Doeppner, T. R. ;
Epple, M. ;
Horn, P. A. ;
Beelen, D. W. ;
Giebel, B. .
LEUKEMIA, 2014, 28 (04) :970-973
[18]   Exosomal vaccines containing the S protein of the SARS coronavirus induce high levels of neutralizing antibodies [J].
Kuate, Seraphin ;
Cinatl, Jindrich ;
Doerr, Hans Wilhelm ;
Uberla, Klaus .
VIROLOGY, 2007, 362 (01) :26-37
[19]  
Lai Ruenn Chai, 2012, Int J Proteomics, V2012, P971907, DOI 10.1155/2012/971907
[20]  
Lai RC, 2011, REGEN MED, V6, P481, DOI [10.2217/RME.11.35, 10.2217/rme.11.35]