Mesenchymal stem cells for treatment of acute and chronic graft-versus-host disease, tissue toxicity and hemorrhages

被引:72
作者
Ringden, O. [1 ]
Le Blanc, K.
机构
[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Ctr Allogene Stem Cell Transplantat,Div Clin Immu, SE-14186 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
Mesenchymal stem cells; Hematopoietic stern cell transplantation; Graft-versus-host disease; Hemorrhagic cystitis; Tissue toxicity; MARROW STROMAL CELLS; LYMPHOCYTE-PROLIFERATION; STEROID-RESISTANT; TRANSPLANTATION; ANTIBODY; CYCLOSPORINE; THERAPY; LEUKEMIA; INHIBIT; METHOTREXATE;
D O I
10.1016/j.beha.2011.01.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mesenchymal stern cells (MSCs) have immunomodulatory effects and low immunogenicity. MSCs inhibit T-cell alloreactivity in vitro. Immune inhibition is caused by soluble factors. MSCs affect almost all cells of the immune system. They are safe to infuse in humans with no acute toxicity and no ectopic tissue formation. We treated patients with life-threatening acute graft-versus-host disease (GVHD) not responding to conventional immunosuppressive therapy with MSCs. Approximately half of the patients responded. HLA-identical or third party MSCs were equally effective. Children tended to have a better response compared to adults. MSCs have also been used for chronic GVHD with positive effects. MSCs also reversed tissue toxicity such as hemorrhagic cystitis, pneumomediastinum and colon perforation with peritonitis. A patient with extensive hemorrhages was successfully treated with repeated doses of MSCs pooled from two donors. This may indicate that MSCs apart from wound healing may stimulate clotting and vasoconstriction. To conclude. MSCs is a novel treatment that may be used for GVHD, tissue toxicity and hemorrhages because of its immune inhibitory and anti-inflammatory effects. (C) 2011 Published by Elsevier Ltd.
引用
收藏
页码:65 / 72
页数:8
相关论文
共 68 条
[1]   Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]  
ANASETTI C, 1994, BLOOD, V84, P1320
[3]  
ATKINSON K, 1982, BLOOD, V60, P714
[4]   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
[5]   Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease [J].
Benito, AI ;
Furlong, T ;
Martin, PJ ;
Anasetti, C ;
Appelbaum, FR ;
Doney, K ;
Nash, RA ;
Papayannopoulou, T ;
Storb, R ;
Sullivan, KM ;
Witherspoon, R ;
Deeg, HJ .
TRANSPLANTATION, 2001, 72 (12) :1924-1929
[6]   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
[7]   Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease [J].
Canninga-van Dijk, MR ;
van der Straaten, HM ;
Fijnheer, R ;
Sanders, CJ ;
van den Tweel, JG ;
Verdonck, LF .
BLOOD, 2004, 104 (08) :2603-2606
[8]   Human mesenchymal stem cells modulate B-cell functions [J].
Corcione, A ;
Benvenuto, F ;
Ferretti, E ;
Giunti, D ;
Cappiello, V ;
Cazzanti, F ;
Risso, M ;
Gualandi, F ;
Mancardi, GL ;
Pistoia, V ;
Uccelli, A .
BLOOD, 2006, 107 (01) :367-372
[9]   Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL [J].
Deeg, HJ ;
Blazar, BR ;
Bolwell, BJ ;
Long, GD ;
Schuening, F ;
Cunningham, J ;
Rifkin, RM ;
Abhyankar, S ;
Briggs, AD ;
Burt, R ;
Lipani, J ;
Roskos, LK ;
White, JM ;
Havrilla, N ;
Schwab, G ;
Heslop, HE .
BLOOD, 2001, 98 (07) :2052-2058
[10]   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