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

页码：35 / 41

页数：7

共 42 条

[1] Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo [J].