Mesenchymal stromal cells to promote solid organ transplantation tolerance

被引:54
作者
Casiraghi, Federica [1 ]
Perico, Norberto [1 ]
Remuzzi, Giuseppe [1 ]
机构
[1] Osped Riuniti Bergamo, Transplant Res Ctr Chiara Cucchi de Alessandri &, Dept Immunol & Transplantat, Mario Negri Inst Pharmacol Res, I-24020 Bergamo, Italy
关键词
effector T cells; kidney transplantation; mesenchymal stromal cells; regulatory T cells; solid organ transplantation; REGULATORY T-CELLS; AUTOIMMUNE MYASTHENIA-GRAVIS; STEM-CELLS; BONE-MARROW; ALLOGRAFT SURVIVAL; LONG-TERM; INDOLEAMINE 2,3-DIOXYGENASE; KIDNEY-TRANSPLANTATION; IMMUNE MODULATION; PROSTAGLANDIN E-2;
D O I
10.1097/MOT.0b013e32835c5016
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review Mesenchymal stromal cells (MSCs) possess unique immunomodulatory features. MSCs dampen effector T-cell response while promoting the emergence of regulatory T cells. By skewing this balance, MSC could represent the ideal strategy for tolerance induction in organ transplantation. Here we review recent evidence on the efficacy of MSC-based therapy in experimental models of solid organ transplantation as well as the early clinical experiences in kidney transplantation. Recent findings MSC infusion in experimental models of solid organ transplantation resulted in a Treg-mediated tolerance. MSC also synergized with low-dose or transient pharmacological immunosuppression in inducing long-term graft survival indicating that these cells could allow safe minimization of maintenance drug therapy. Early results from clinical studies in kidney transplant recipients reported encouraging results on the immunoregulatory effect of MSC, although posttransplant MSC infusion could associate with acute graft dysfunction (engraftment syndrome). Summary Immunoregulatory functions of MSC are not fixed but rather the result of microenvironment they encounter in vivo. Further studies are needed to establish how and wherein these cells have to be administered and how they may function to safely modulate host immune response in vivo in clinical transplant setting.
引用
收藏
页码:51 / 58
页数:8
相关论文
共 78 条
[61]   Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells [J].
Selmani, Zohair ;
Naji, Abderrahim ;
Zidi, Ines ;
Favier, Benoit ;
Gaiffe, Emilie ;
Obert, Laurent ;
Borg, Christophe ;
Saas, Philippe ;
Tiberghien, Pierre ;
Rouas-Freiss, Nathalie ;
Carosella, Edgardo D. ;
Deschaseaux, Frederic .
STEM CELLS, 2008, 26 (01) :212-222
[62]   Human adipose tissue-derived mesenchymal stem cells facilitate the immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1-mediated inhibition of NF-κB signaling [J].
Shi, Dan ;
Liao, Lianming ;
Zhang, Bin ;
Liu, Rui ;
Dou, Xiaowei ;
Li, Jing ;
Zhu, Xishan ;
Yu, Limei ;
Chen, Daixiong ;
Zhao, Robert C. H. .
EXPERIMENTAL HEMATOLOGY, 2011, 39 (02) :214-224
[63]   Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia [J].
Solari, Mario G. ;
Srinivasan, Suganya ;
Boumaza, Imene ;
Unadkat, Jignesh ;
Harb, George ;
Garcia-Ocana, Adolfo ;
Feili-Hariri, Maryam .
JOURNAL OF AUTOIMMUNITY, 2009, 32 (02) :116-124
[64]   Mesenchymal Stem Cell Transplantation Reverses Multiorgan Dysfunction in Systemic Lupus Erythematosus Mice and Humans [J].
Sun, Lingyun ;
Akiyama, Kentaro ;
Zhang, Huayong ;
Yamaza, Takayoshi ;
Hou, Yayi ;
Zhao, Shengnan ;
Xu, Ting ;
Le, Anh ;
Shi, Songtao .
STEM CELLS, 2009, 27 (06) :1421-1432
[65]   The Role of Mouse Mesenchymal Stem Cells in Differentiation of Naive T-Cells into Anti-Inflammatory Regulatory T-Cell or Proinflammatory Helper T-Cell 17 Population [J].
Svobodova, Eliska ;
Krulova, Magdalena ;
Zajicova, Alena ;
Pokorna, Katerina ;
Prochazkova, Jana ;
Trosan, Peter ;
Holan, Vladimir .
STEM CELLS AND DEVELOPMENT, 2012, 21 (06) :901-910
[66]   Induction Therapy With Autologous Mesenchymal Stem Cells in Living-Related Kidney Transplants A Randomized Controlled Trial [J].
Tan, Jianming ;
Wu, Weizhen ;
Xu, Xiumin ;
Liao, Lianming ;
Zheng, Feng ;
Messinger, Shari ;
Sun, Xinhui ;
Chen, Jin ;
Yang, Shunliang ;
Cai, Jinquan ;
Gao, Xia ;
Pileggi, Antonello ;
Ricordi, Camillo .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2012, 307 (11) :1169-1177
[67]   Bone Marrow-Derived Mesenchymal Stem Cells Inhibit Acute Rejection of Rat Liver Allografts in Association With Regulatory T-Cell Expansion [J].
Wang, Y. ;
Zhang, A. ;
Ye, Z. ;
Xie, H. ;
Zheng, S. .
TRANSPLANTATION PROCEEDINGS, 2009, 41 (10) :4352-4356
[68]   Low-dose of tacrolimus favors the induction of functional CD4+CD25+FoxP3+ regulatory T cells in solid-organ transplantation [J].
Wang, Zhen ;
Shi, Bingyi ;
Jin, Hailong ;
Xiao, Li ;
Chen, Yongwei ;
Qian, Yeyong .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2009, 9 (05) :564-569
[69]   Regulatory T cells in transplantation tolerance [J].
Wood, KJ ;
Sakaguchi, S .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (03) :199-210
[70]   Mesenchymal stem cells differentially mediate regulatory T cells and conventional effector T cells to protect fully allogeneic islet grafts in mice [J].
Xu, D. M. ;
Yu, X. F. ;
Zhang, D. ;
Zhang, M. X. ;
Zhou, J. F. ;
Tan, P. H. ;
Ding, Y. C. .
DIABETOLOGIA, 2012, 55 (04) :1091-1102