Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease

被引:534
作者
Yanez, Rosa
Lamana, Maria Luisa
Garcia-Castro, Javier
Colmenero, Isabel
Ramirez, Manuel
Bueren, Juan A.
机构
[1] CIEMAT, Hematopoiesis & Gene Therapy Div, Marcelino Botin Fdn, E-28040 Madrid, Spain
[2] Hosp Nino Jesus, Pediat Hematol & Oncol & Hematopoiet Transplant U, Madrid, Spain
[3] Hosp Nino Jesus, Dept Pathol, Madrid, Spain
关键词
stem cell transplantation; graft-versus-host disease; immunosuppression; mesenchymal stem cells; experimental model; BONE-MARROW TRANSPLANTATION; CORD BLOOD; T-CELLS; PROLIFERATION; LEUKEMIA; LYMPHOCYTES; EXPRESSION; INHIBIT; PHASE; VITRO;
D O I
10.1634/stemcells.2006-0228
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Previous studies have shown the relevance of bone marrow-derived MSCs (BM-MSCs) in controlling graft-versus-host disease (GVHD) after allogeneic transplantation. Since adipose tissue-derived MSCs (Ad-MSCs) may constitute a good alternative to BM-MSCs, we have expanded MSCs derived from human adipose tissue (hAd-MSCs) and mouse adipose tissue (mAd-MSCs), investigated the immunoregulatory properties of these cells, and evaluated their capacity to control GVHD in mice. The phenotype and immunoregulatory properties of expanded hAd-MSCs were similar to those of human BM-MSCs. Moreover, hAd-MSCs inhibited the proliferation and cytokine secretion of human primary T cells in response to mitogens and allogeneic T cells. Similarly, ex vivo expanded mAd-MSCs had an equivalent immunophenotype and exerted immunoregulatory properties similar to those of hAd-MSCs. Moreover, the infusion of mAd-MSCs in mice transplanted with haploidentical hematopoietic grafts controlled the lethal GVHD that occurred in control recipient mice. These findings constitute the first experimental proof that Ad-MSCs can efficiently control the GVHD associated with allogeneic hematopoietic transplantation, opening new perspectives for the clinical use of Ad-MSCs.
引用
收藏
页码:2582 / 2591
页数:10
相关论文
共 34 条
[1]   Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]   Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo [J].
Bartholomew, A ;
Sturgeon, C ;
Siatskas, M ;
Ferrer, K ;
McIntosh, K ;
Patil, S ;
Hardy, W ;
Devine, S ;
Ucker, D ;
Deans, R ;
Moseley, A ;
Hoffman, R .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (01) :42-48
[3]   Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness [J].
Beyth, S ;
Borovsky, Z ;
Mevorach, D ;
Liebergall, M ;
Gazit, Z ;
Aslan, H ;
Galun, E ;
Rachmilewitz, J .
BLOOD, 2005, 105 (05) :2214-2219
[4]   HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia [J].
Bonini, C ;
Ferrari, G ;
Verzeletti, S ;
Servida, P ;
Zappone, E ;
Ruggieri, L ;
Ponzoni, M ;
Rossini, S ;
Mavilio, F ;
Traversari, C ;
Bordignon, C .
SCIENCE, 1997, 276 (5319) :1719-1724
[5]   Dedifferentiated adult articular chondrocytes:: a population of human multipotent primitive cells [J].
de la Fuente, R ;
Abad, JL ;
García-Castro, J ;
Fernández-Miguel, G ;
Petriz, J ;
Rubio, D ;
Vicario-Abejón, C ;
Guillén, P ;
González, MA ;
Bernad, A .
EXPERIMENTAL CELL RESEARCH, 2004, 297 (02) :313-328
[6]   Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates [J].
Devine, SM ;
Cobbs, C ;
Jennings, M ;
Bartholomew, A ;
Hoffman, R .
BLOOD, 2003, 101 (08) :2999-3001
[7]   Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli [J].
Di Nicola, M ;
Carlo-Stella, C ;
Magni, M ;
Milanesi, M ;
Longoni, PD ;
Matteucci, P ;
Grisanti, S ;
Gianni, AM .
BLOOD, 2002, 99 (10) :3838-3843
[8]   Haemopoietic stem-cell transplantation: improving immune reconstitution, avoiding graft-versus-host disease [J].
Dickinson, A ;
Cant, A .
LANCET, 2002, 360 (9327) :98-99
[9]   Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals [J].
Djouad, F ;
Plence, P ;
Bony, C ;
Tropel, P ;
Apparailly, F ;
Sany, J ;
Noël, D ;
Jorgensen, C .
BLOOD, 2003, 102 (10) :3837-3844
[10]   Mesenchymal progenitor cells in human umbilical cord blood [J].
Erices, A ;
Conget, P ;
Minguell, JJ .
BRITISH JOURNAL OF HAEMATOLOGY, 2000, 109 (01) :235-242