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
[11]   Localization of Mesenchymal Stromal Cells Dictates Their Immune or Proinflammatory Effects in Kidney Transplantation [J].
Casiraghi, F. ;
Azzollini, N. ;
Todeschini, M. ;
Cavinato, R. A. ;
Cassis, P. ;
Solini, S. ;
Rota, C. ;
Morigi, M. ;
Introna, M. ;
Maranta, R. ;
Perico, N. ;
Remuzzi, G. ;
Noris, M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2012, 12 (09) :2373-2383
[12]   Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells [J].
Casiraghi, Federica ;
Azzollini, Nadia ;
Cassis, Paola ;
Imberti, Barbara ;
Morigi, Marina ;
Cugini, Daniela ;
Cavinato, Regiane Aparecida ;
Todeschini, Marta ;
Solini, Samantha ;
Sonzogni, Aurelio ;
Perico, Norberto ;
Remuzzi, Giuseppe ;
Noris, Marina .
JOURNAL OF IMMUNOLOGY, 2008, 181 (06) :3933-3946
[13]   A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells [J].
Chabannes, Dominique ;
Hill, Marcelo ;
Merieau, Emmanuel ;
Rossignol, Julien ;
Brion, Regis ;
Soulillou, Jean Paul ;
Anegon, Ignacio ;
Cuturi, Maria Cristina .
BLOOD, 2007, 110 (10) :3691-3694
[14]   Mesenchymal stem cells reside in virtually all post-natal organs and tissues [J].
da Silva Meirelles, Lindolfo ;
Chagastelles, Pedro Cesar ;
Nardi, Nance Beyer .
JOURNAL OF CELL SCIENCE, 2006, 119 (11) :2204-2213
[15]   Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor? [J].
de Lafaille, Maria A. Curotto ;
Lafaille, Juan J. .
IMMUNITY, 2009, 30 (05) :626-635
[16]   Mesenchymal cells recruit and regulate T regulatory cells [J].
Di Lanni, Mauro ;
Del Papa, Beatrice ;
De Loanni, Maria ;
Moretti, Lorenzo ;
Bonifacio, Elisabetta ;
Cecchini, Debora ;
Sportoletti, Paolo ;
Falzetti, Franca ;
Tabilio, Antonio .
EXPERIMENTAL HEMATOLOGY, 2008, 36 (03) :309-318
[17]   Mesenchymal Stem Cells Prevent the Rejection of Fully Allogenic Islet Grafts by the Immunosuppressive Activity of Matrix Metalloproteinase-2 and-9 [J].
Ding, Yunchuan ;
Xu, Danmei ;
Feng, Gang ;
Bushell, Andrew ;
Muschel, Ruth J. ;
Wood, Kathryn J. .
DIABETES, 2009, 58 (08) :1797-1806
[18]   Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].
Dominici, M. ;
Le Blanc, K. ;
Mueller, I. ;
Slaper-Cortenbach, I. ;
Marini, F. C. ;
Krause, D. S. ;
Deans, R. J. ;
Keating, A. ;
Prockop, D. J. ;
Horwitz, E. M. .
CYTOTHERAPY, 2006, 8 (04) :315-317
[19]   Mesenchymal stem cell effects on T-cell effector pathways [J].
Duffy, Michelle M. ;
Ritter, Thomas ;
Ceredig, Rhodri ;
Griffin, Matthew D. .
STEM CELL RESEARCH & THERAPY, 2011, 2
[20]   Features of synergism between mesenchymal stem cells and immunosuppressive drugs in a murine heart transplantation model [J].
Eggenhofer, Elke ;
Renner, Philipp ;
Soeder, Yorick ;
Popp, Felix C. ;
Hoogduijn, Martin J. ;
Geissler, Edward K. ;
Schlitt, Hans J. ;
Dahlke, Marc H. .
TRANSPLANT IMMUNOLOGY, 2011, 25 (2-3) :141-147