Human umbilical cord mesenchymal stem cells protect against ischemic brain injury in mouse by regulating peripheral immunoinflammation

被引:53
作者
Cheng, Qiantao [1 ,2 ]
Zhang, Zhuo [1 ,3 ,4 ]
Zhang, Shenyang [1 ,3 ,4 ]
Yang, Hui [1 ,3 ,4 ]
Zhang, Xin [1 ,3 ,4 ]
Pan, Jie [1 ,3 ,4 ]
Weng, Leihua [1 ,3 ,4 ]
Sha, Dujuan [1 ,3 ,4 ]
Zhu, Min [1 ,6 ]
Hu, Xiang [7 ]
Xu, Yun [1 ,3 ,4 ,5 ]
机构
[1] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Huaian Peoples Hosp 1, Dept Neurol, Huaian, Jiangsu, Peoples R China
[3] Nanjing Univ, Sch Med, Jiangsu Key Lab Mol Med, Nanjing 210008, Jiangsu, Peoples R China
[4] Jiangsu Prov Stroke Ctr Diag & Therapy, Huaian, Peoples R China
[5] Nanjing Neuropsychiat Clin Med Ctr, Nanjing, Jiangsu, Peoples R China
[6] Nanjing Med Univ, Nanjing Childrens Hosp, Dept Neurol & Rehabil, Nanjing, Jiangsu, Peoples R China
[7] Shenzhen Beike Stem Cell Engn Inst, Shenzhen, Peoples R China
基金
中国国家自然科学基金;
关键词
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs); Stroke; Neuroimmunology; Transplantation; GROWTH-FACTOR-BETA; T-CELLS; INFLAMMATORY MECHANISMS; IMMUNE-RESPONSES; STROMAL CELLS; TGF-BETA; STROKE; DIFFERENTIATION; INDUCTION; PATHWAYS;
D O I
10.1016/j.brainres.2014.10.065
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
Current treatments for ischemic stroke are limited, stem cell transplantation offers great potential as a therapeutic strategy. The present study was undertaken to determine whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could improve brain injury after middle cerebral artery occlusion (MCAO) through modulating peripheral immunoinflammation. The study showed that neurological deficit was ameliorated and brain edema, infarct volume was significantly decreased from 72 h to 1 week post-MCAO with hUC-MSCs treatment via tail vein injection within 30 mins after stroke; hUC-MSCs attenuated the levels of inflammatory factors including IL-1, TNF-alpha, IL-23, IL-17 and IL-10 in peripheral blood serum and ischemia hemisphere after stroke; hUC-MSCs significantly decreased the level of Th17 cells at 24 h and increased the level of Tregs at 72 h post-MCAO in peripheral immune system; the level of TGF-beta in blood serum was enhanced by hUC-MSCs. In conclusion, our findings suggested that hUC-MSCs had neuroprotection in MCAO mice by TGF-beta modulating peripheral immune and hUC-MSCs may be as a potential therapy for ischemic stroke. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:293 / 304
页数:12
相关论文
共 49 条
[1]
Antitransforming growth factor-β antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation [J].
Anscher, MS ;
Thrasher, B ;
Rabbani, Z ;
Teicher, B ;
Vujaskovic, Z .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 65 (03) :876-881
[2]
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[3]
Umbilical Cord-Derived Mesenchymal Stem Cells for Hematopoietic Stem Cell Transplantation [J].
Chao, Yu-Hua ;
Wu, Han-Ping ;
Chan, Chin-Kan ;
Tsai, Chris ;
Peng, Ching-Tien ;
Wu, Kang-Hsi .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2012,
[4]
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3 [J].
Chen, WJ ;
Jin, WW ;
Hardegen, N ;
Lei, KJ ;
Li, L ;
Marinos, N ;
McGrady, G ;
Wahl, SM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) :1875-1886
[5]
Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis [J].
Chen, Y ;
Langrish, CL ;
Mckenzie, B ;
Joyce-Shaikh, B ;
Stumhofer, JS ;
McClanahan, T ;
Blumenschein, W ;
Churakovsa, T ;
Low, J ;
Presta, L ;
Hunter, CA ;
Kastelein, RA ;
Cua, DJ .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (05) :1317-1326
[6]
Human urinary kallidinogenase suppresses cerebral inflammation in experimental stroke and downregulates nuclear factor-κB [J].
Chen, Zhi-bin ;
Huang, Dan-qing ;
Niu, Feng-nan ;
Zhang, Xin ;
Li, Er-guang ;
Xu, Yun .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2010, 30 (07) :1356-1365
[7]
Enhancement of neuroplasticity through upregulation of β1-integrin in human umbilical cord-derived stromal cell implanted stroke model [J].
Ding, Dah-Ching ;
Shyu, Woei-Cherng ;
Chiang, Ming-Fu ;
Lin, Shinn-Zong ;
Chang, Ying-Chen ;
Wang, Hslao-Jung ;
Su, Ching-Yuan ;
Li, Hung .
NEUROBIOLOGY OF DISEASE, 2007, 27 (03) :339-353
[8]
Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke [J].
Gelderblom, Mathias ;
Weymar, Anna ;
Bernreuther, Christian ;
Velden, Joachim ;
Arunachalam, Priyadharshini ;
Steinbach, Karin ;
Orthey, Ellen ;
Arumugam, Thiruma V. ;
Leypoldt, Frank ;
Simova, Olga ;
Thom, Vivien ;
Friese, Manuel A. ;
Prinz, Immo ;
Hoelscher, Christoph ;
Glatzel, Markus ;
Korn, Thomas ;
Gerloff, Christian ;
Tolosa, Eva ;
Magnus, Tim .
BLOOD, 2012, 120 (18) :3793-3802
[9]
Key molecules in the differentiation and commitment program of T helper 17 (Th17) cells up-to-date [J].
Hemdan, Nasr Y. A. ;
Birkenmeier, Gerd ;
Wichmann, Gunnar .
IMMUNOLOGY LETTERS, 2012, 148 (02) :97-109
[10]
Hetman M, 2000, J NEUROSCI, V20, P2567