Cell therapy for autoimmune diseases

被引:70
作者
Dazzi, Francesco [1 ]
van Laar, Jacob M.
Cope, Andrew
Tyndall, Alan
机构
[1] Imperial Coll Fac Med, Kennedy Inst Rheumatol, Stem Cell Biol Sect, London, England
[2] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands
[3] Univ Basel, Felix Plattel Spital, Dept Rheumatol, Basel, Switzerland
关键词
MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; REGULATORY T-CELLS; HIGH-DOSE CHEMOTHERAPY; REFRACTORY RHEUMATOID-ARTHRITIS; IMMUNOLOGICAL SELF-TOLERANCE; MYELOID SUPPRESSOR-CELLS; VERSUS-HOST-DISEASE; SYSTEMIC-LUPUS; IMMUNOSUPPRESSIVE THERAPY;
D O I
10.1186/ar2128
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immunosuppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases.
引用
收藏
页数:9
相关论文
共 106 条
[1]   Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]   An epigenetic view of helper T cell differentiation [J].
Ansel, KM ;
Lee, DU ;
Rao, A .
NATURE IMMUNOLOGY, 2003, 4 (07) :616-623
[3]   The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells [J].
Barry, F ;
Boynton, R ;
Murphy, M ;
Zaia, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 289 (02) :519-524
[4]   The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105) [J].
Barry, FP ;
Boynton, RE ;
Haynesworth, S ;
Murphy, JM ;
Zaia, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 265 (01) :134-139
[5]   T cell regulation as a side effect of homeostasis and competition [J].
Barthlott, T ;
Kassiotis, G ;
Stockinger, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (04) :451-460
[6]   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
[7]   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
[8]   Phase I/II trial of autologous stem cell transplantation in systemic sclerosis:: procedure related mortality and impact on skin disease [J].
Binks, M ;
Passweg, JR ;
Furst, D ;
McSweeney, P ;
Sullivan, K ;
Besenthal, C ;
Finke, J ;
Peter, HH ;
van Laar, J ;
Breedveld, FC ;
Fibbe, VE ;
Farge, D ;
Gluckman, E ;
Locatelli, F ;
Martini, A ;
van den Hoogen, F ;
van de Putte, L ;
Schattenberg, AVN ;
Arnold, R ;
Bacon, PA ;
Emery, P ;
Espigado, I ;
Hertenstein, B ;
Hiepe, F ;
Kashyap, A ;
Kötter, I ;
Marmont, A ;
Martinez, A ;
Pascual, MJ ;
Gratwohl, A ;
Prentice, HG ;
Black, C ;
Tyndall, A .
ANNALS OF THE RHEUMATIC DISEASES, 2001, 60 (06) :577-584
[9]   Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro [J].
Bocelli-Tyndall, C. ;
Bracci, L. ;
Spagnoli, G. ;
Braccini, A. ;
Bouchenaki, M. ;
Ceredig, R. ;
Pistoia, V. ;
Martin, I. ;
Tyndall, A. .
RHEUMATOLOGY, 2007, 46 (03) :403-408
[10]   T-CELL TOLERANCE BY CLONAL ANERGY IN TRANSGENIC MICE WITH NONLYMPHOID EXPRESSION OF MHC CLASS-II I-E [J].
BURKLY, LC ;
LO, D ;
KANAGAWA, O ;
BRINSTER, RL ;
FLAVELL, RA .
NATURE, 1989, 342 (6249) :564-566