Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC treatment of stroke

被引：70
作者：
Cui, Xu [1 ]
Chopp, Michael [1 ,4 ]
Zacharek, Alex [1 ]
Roberts, Cynthia [1 ]
Lu, Mei [2 ]
Savant-Bhonsale, Smita [3 ]
Chen, Jieli [1 ]
机构：
[1] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
[2] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA
[3] Theradigm Inc, Dept Neurobiol, Baltimore, MD 21227 USA
[4] Oakland Univ, Dept Phys, Rochester, MI 48309 USA
来源：
NEUROBIOLOGY OF DISEASE | 2009年 / 36卷 / 01期
关键词：
Bone marrow stromal cell; Simvastatin; Arteriogenesis; Angiogenesis; Stroke; MARROW STROMAL CELLS; ARTERY GROWTH ARTERIOGENESIS; ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; NITRIC-OXIDE DONOR; IN-VIVO; MYOCARDIAL-INFARCTION; PARACRINE MECHANISMS; CEREBRAL-ISCHEMIA; ANGIOGENESIS;
D O I：
10.1016/j.nbd.2009.06.012
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
We investigated the additive therapeutic effect of the combination treatment of stroke with sub-therapeutic doses of Simvastatin, a HMG-CoA reductase inhibitor, and bone marrow stromal cells (BMSCs). Rats were administered Simvastatin (0.5 mg/kg), BMSCs (1x10(6)) or combination of Simvastatin and BMSCs starting at 24 h after stroke. Combination treatment significantly improved neurological outcome, enhanced angiogenesis and arteriogenesis, and increased the number of engrafted-BMSCs in the ischemic brain. The number of engrafted-BMSCs and arteriogenesis was significantly correlated with functional outcome. Simvastatin significantly increased stromal cell-derived factor-1 (SDF1) expression in the ischemic brain and chemokine (CXC motif) receptor-4 (CXCR4) in BMSCs, and increased BMSC migration to RBMECs and astrocytes. Combination treatment of stroke upregulates the SDF1/CXCR4 axis and enhances BMSC migration into the ischemic brain, amplifies arteriogenesis and angiogenesis, and improves functional outcome after stroke. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码：35 / 41
页数：7
相关论文
共 42 条
[11]   Neurorestorative Treatment of Stroke: Cell and Pharmacological Approaches [J].
Chen J. ;
Chopp M. .
NeuroRX, 2006, 3 (4) :466-473
[12]   Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice [J].
Chen, JL ;
Zhang, CL ;
Jiang, H ;
Li, Y ;
Zhang, LJ ;
Robin, A ;
Katakowski, M ;
Lu, M ;
Chopp, M .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2005, 25 (02) :281-290
[13]   Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke [J].
Chen, JL ;
Zhang, ZG ;
Li, Y ;
Wang, Y ;
Wang, L ;
Jiang, H ;
Zhang, CL ;
Lu, M ;
Katakowski, M ;
Feldkamp, CS ;
Chopp, M .
ANNALS OF NEUROLOGY, 2003, 53 (06) :743-751
[14]   Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis [J].
Chen, JL ;
Li, Y ;
Zhang, RL ;
Katakowski, M ;
Gautam, SC ;
Xu, YX ;
Lu, M ;
Zhang, ZG ;
Chopp, M .
BRAIN RESEARCH, 2004, 1005 (1-2) :21-28
[15]   Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats [J].
Chen, JL ;
Zhang, ZG ;
Li, Y ;
Wang, L ;
Xu, YX ;
Gautam, SC ;
Lu, M ;
Zhu, Z ;
Chopp, M .
CIRCULATION RESEARCH, 2003, 92 (06) :692-699
[16]   Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats [J].
Chen, JL ;
Li, Y ;
Wang, L ;
Zhang, ZG ;
Lu, DY ;
Lu, M ;
Chopp, M .
STROKE, 2001, 32 (04) :1005-1011
[17]  
Christoforidis GA, 2005, AM J NEURORADIOL, V26, P1789
[18]   A perivascular origin for mesenchymal stem cells in multiple human organs [J].
Crisan, Mihaela ;
Yap, Solomon ;
Casteilla, Louis ;
Chen, Chien-Wen ;
Corselli, Mirko ;
Park, Tea Soon ;
Andriolo, Gabriella ;
Sun, Bin ;
Zheng, Bo ;
Zhang, Li ;
Norotte, Cyrille ;
Teng, Pang-Ning ;
Traas, Jeremy ;
Schugar, Rebecca ;
Deasy, Bridget M. ;
Badylak, Stephen ;
Buehring, Hans-Joerg ;
Giacobino, Jean-Paul ;
Lazzari, Lorenza ;
Huard, Johnny ;
Peault, Bruno .
CELL STEM CELL, 2008, 3 (03) :301-313
[19]   Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization [J].
Cui, X. ;
Chen, J. ;
Zacharek, A. ;
Roberts, C. ;
Savant-Bhonsale, S. ;
Chopp, M. .
NEUROSCIENCE, 2008, 156 (01) :155-164
[20]   ROLE OF ENDOTHELIAL NITRIC OXIDE SYNTHETASE IN ARTERIOGENESIS AFTER STROKE IN MICE [J].
Cui, X. ;
Chopp, M. ;
Zacharek, A. ;
Zhang, C. ;
Roberts, C. ;
Chen, J. .
NEUROSCIENCE, 2009, 159 (02) :744-750
12345