Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft

被引:120
作者
Zhou, H. P. [1 ]
Yi, D. H. [1 ]
Yu, S. Q. [1 ]
Sun, G. C. [1 ]
Cui, Q. [1 ]
Zhu, H. L. [1 ]
Liu, J. C. [1 ]
Zhang, J. Z. [1 ]
Wu, T. J. [1 ]
机构
[1] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiovasc Surg, Xian 710032, Shannxi Prov, Peoples R China
关键词
D O I
10.1016/j.transproceed.2006.10.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Mesenchymal stem cells (MSCs) are multipotent adult elements that have recently been shown to have profound immunomodulatory effects both in vitro and in vivo. Herein we have examined the impact of intravenous infusion of donor MSCs on the survival of transplanted hearts in a rat allograft model. Methods. Recipient Fisher344 rats were transplanted with hearts from inbred Wistar rats. Wistar rat MSCs were infused via the tail vein at designated intervals. In vitro mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays were performed to assess whether MSCs downregulated T-cell responses in vivo. Real-time polymerase chain reaction (PCR) was used to analyze the Th1/Th2 balance in MSC-treated and control groups. Results. The MSCs cultured in vitro exhibited multipotential for differentiation. Survival of the allografts was markedly prolonged by administration of MSCs compared with the controls, namely mean survivals of 12.4 vs 6.4 days, respectively. Real-time PCR showed a shift in the Th1/Th2 balance toward Th2. By MLR and CML assays, untreated control rats showed greater alloreactivity than did MSC-treated rats. Conclusion. Our results indicated that MSCs suppressed allogeneic T-cell responses both in vitro and in vivo. Intravenous administration of MSCs prolonged the survival of transplanted hearts, possibly by induction of allograft tolerance through changing the Th1/Th2 balance.
引用
收藏
页码:3046 / 3051
页数:6
相关论文
共 27 条
[1]   Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]   Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice [J].
Allers, C ;
Sierralta, WD ;
Neubauer, S ;
Rivera, F ;
Minguell, JJ ;
Conget, PA .
TRANSPLANTATION, 2004, 78 (04) :503-508
[3]   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
[4]   Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction [J].
Chen, SL ;
Fang, W ;
Ye, F ;
Liu, YH ;
Qian, J ;
Shan, S ;
Zhang, J ;
Zhao, RCH ;
Liao, LM ;
Lin, S ;
Sun, JP .
AMERICAN JOURNAL OF CARDIOLOGY, 2004, 94 (01) :92-95
[5]   PRIMARILY VASCULARIZED ALLOGRAFTS OF HEARTS IN MICE - ROLE OF H-2D, H-2K, AND NON-H-2 ANTIGENS IN REJECTION [J].
CORRY, RJ ;
WINN, HJ ;
RUSSELL, PS .
TRANSPLANTATION, 1973, 16 (04) :343-350
[6]   Immunosuppressive strategies in transplantation [J].
Denton, MD ;
Magee, CC ;
Sayegh, MH .
LANCET, 1999, 353 (9158) :1083-1091
[7]   Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion [J].
Devine, SM ;
Bartholomew, AM ;
Mahmud, N ;
Nelson, M ;
Patil, S ;
Hardy, W ;
Sturgeon, C ;
Hewett, T ;
Chung, T ;
Stock, W ;
Sher, D ;
Weissman, S ;
Ferrer, K ;
Mosca, J ;
Deans, R ;
Moseley, A ;
Hoffman, R .
EXPERIMENTAL HEMATOLOGY, 2001, 29 (02) :244-255
[8]   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
[9]   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
[10]   Different in vivo tolerogenicity of MHC class I peptides [J].
Fändrich, F ;
Zhu, XF ;
Schröder, J ;
Dresske, B ;
Henne-Bruns, D ;
Oswald, H ;
Zavazava, N .
JOURNAL OF LEUKOCYTE BIOLOGY, 1999, 65 (01) :16-27