Mesenchymal Stem Cells Ameliorate Th1-Induced Pre-Eclampsia-Like Symptoms in Mice via the Suppression of TNF-α Expression

被引:51
作者
Liu, Liu [1 ,2 ]
Zhao, Guangfeng [1 ,2 ]
Fan, Hongye [1 ,2 ]
Zhao, Xiaoyin [1 ,2 ]
Li, Pengfei [1 ,2 ]
Wang, Zhiqun [3 ]
Hu, Yali [3 ]
Hou, Yayi [1 ,2 ,4 ]
机构
[1] Nanjing Univ, Sch Med, Immunol Lab, Nanjing 210008, Jiangsu, Peoples R China
[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Jiangsu, Peoples R China
[3] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China
[4] Jiangsu Key Lab Mol Med, Nanjing, Jiangsu, Peoples R China
关键词
NECROSIS-FACTOR-ALPHA; AGONISTIC AUTOANTIBODIES; MOUSE MODEL; RAT MODEL; PREECLAMPSIA; HYPERTENSION; CYTOKINES; RECEPTOR; IMBALANCE; PROTECT;
D O I
10.1371/journal.pone.0088036
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pre-eclampsia (PE) is thought to be a pregnancy-induced autoimmune disease. Despite several strategies carried out for targeting specific factors relevant to its pathogenesis, PE remains potentially fatal to some patients. Here, we reported a way to isolate mesenchymal stem cells (MSCs) from decidua. The MSCs not only exhibited differentiation and self-renewal capacities, they also possessed immunomodulatory functions and secreted some soluble mediators including IL-6, TGF-beta, IDO, VEGF and COX-2. Most importantly, the MSCs were specifically provided with the ability to suppress T cells proliferation by IDO in response to inflammatory cytokine IFN-gamma. Moreover, we developed a Th1 cell-induced PE mouse model which displayed a high level of pathogenesis factor TNF-alpha. Strikingly, MSCs-based therapy significantly ameliorated both clinical and histopathological severity of PE symptoms including decreasing the blood pressure and proteinuria, suppressing glomerulonephritis, protecting the feto-placental development. The therapy also reversed abnormal TNF-alpha expression in uterine and splenic lymphocytes. These data suggest that MSCs may ameliorate Th1-induced PE-like symptoms in mice via the suppression of TNF-alpha and MSCs-based therapy may provide a potential novel method for PE.
引用
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页数:10
相关论文
共 45 条
[1]   Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]   Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling [J].
Aicher, A ;
Brenner, W ;
Zuhayra, M ;
Badorff, C ;
Massoudi, S ;
Assmus, B ;
Eckey, T ;
Henze, E ;
Zeiher, AM ;
Dimmeler, S .
CIRCULATION, 2003, 107 (16) :2134-2139
[3]   sFRP2 Suppression of Bone Morphogenic Protein (BMP) and Wnt Signaling Mediates Mesenchymal Stem Cell (MSC) Self-renewal Promoting Engraftment and Myocardial Repair [J].
Alfaro, Maria P. ;
Vincent, Alicia ;
Saraswati, Sarika ;
Thorne, Curtis A. ;
Hong, Charles C. ;
Lee, Ethan ;
Young, Pampee P. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (46) :35645-35653
[4]  
Carter D, 2005, BLOOD, V106, p160B
[5]  
Conrad KP, 1998, AM J REPROD IMMUNOL, V40, P102
[6]  
Conrad KP, 1997, AM J REPROD IMMUNOL, V37, P240
[7]   T helper 1-and T helper 2-type cytokine imbalance in pregnant women with pre-eclampsia [J].
Darmochwal-Kolarz, D ;
Leszczynska-Gorzelak, B ;
Rolinski, J ;
Oleszczuk, J .
EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 1999, 86 (02) :165-170
[8]   Placental imbalance of Th1- and Th2-type cytokines in preeclampsia [J].
Dong, MY ;
He, J ;
Wang, ZP ;
Xie, X ;
Wang, HZ .
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 2005, 84 (08) :788-793
[9]   Examination of distinct fetal and maternal molecular pathways suggests a mechanism for the development of preeclampsia [J].
Goldman-Wohl, Debra S. ;
Yagel, Simcha .
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2007, 76 (1-2) :54-60
[10]   Treatment of Experimental Arthritis by Inducing Immune Tolerance With Human Adipose-Derived Mesenchymal Stem Cells [J].
Gonzalez, Manuel A. ;
Gonzalez-Rey, Elena ;
Rico, Laura ;
Buescher, Dirk ;
Delgado, Mario .
ARTHRITIS AND RHEUMATISM, 2009, 60 (04) :1006-1019