共 60 条
MiR-126 Contributes to Human Umbilical Cord Blood Cell-Induced Neurorestorative Effects After Stroke in Type-2 Diabetic Mice
被引:63
作者:

Chen, Jieli
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机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
Tianjin Med Univ, Gen Hosp, Tianjin Geriatr Inst, Dept Geriatr, Tianjin, Peoples R China Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Ning, Ruizhuo
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机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Zacharek, Alex
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机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Cui, Chengcheng
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机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Cui, Xu
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h-index: 0
机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Yan, Tao
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机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Venkat, Poornima
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h-index: 0
机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
Oakland Univ, Dept Phys, Rochester, MI USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Zhang, Yi
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h-index: 0
机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA

Chopp, Michael
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h-index: 0
机构:
Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
Oakland Univ, Dept Phys, Rochester, MI USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
机构:
[1] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
[2] Tianjin Med Univ, Gen Hosp, Tianjin Geriatr Inst, Dept Geriatr, Tianjin, Peoples R China
[3] Oakland Univ, Dept Phys, Rochester, MI USA
来源:
关键词:
microRNA126;
Human umbilical cord blood cell;
Type-2;
diabetes;
White matter;
Stroke;
IMPROVES FUNCTIONAL RECOVERY;
NEURAL PROGENITOR CELLS;
MESENCHYMAL STEM-CELLS;
ACUTE ISCHEMIC-STROKE;
WHITE-MATTER;
PLASMINOGEN-ACTIVATOR;
M2;
MACROPHAGES;
MICROGLIA/MACROPHAGE POLARIZATION;
VASCULAR STABILIZATION;
ADOPTIVE TRANSFER;
D O I:
10.1002/stem.2193
中图分类号:
Q813 [细胞工程];
学科分类号:
摘要:
Diabetes mellitus (DM) is a high risk factor for stroke and leads to more severe vascular and white-matter injury than stroke in non-DM. We tested the neurorestorative effects of delayed human umbilical cord blood cell (HUCBC) treatment of stroke in type-2 diabetes (T2DM). db/db-T2DM and db/+-non-DM mice were subjected to distal middle cerebral artery occlusion (dMCAo) and were treated 3 days after dMCAo with: (a) non-DM + Phosphate buffered saline (PBS); (b) T2DM + PBS; (c) T2DM + naive-HUCBC; (d) T2DM + miR-126(-/-) HUCBC. Functional evaluation, vascular and white-matter changes, neuroinflammation, and miR-126 effects were measured in vivo and in vitro. T2DM mice exhibited significantly decreased serum and brain tissue miR-126 expression compared with non-DM mice. T2DM + HUCBC mice exhibited increased miR-126 expression, increased tight junction protein expression, axon/myelin, vascular density, and M2-macrophage polarization. However, decreased blood-brain barrier leakage, brain hemorrhage, and miR-126 targeted gene vascular cell adhesion molecule-1 and monocyte chemotactic protein 1 expression in the ischemic brain as well as improved functional outcome were present in HUCBC-treated T2DM mice compared with control T2DM mice. MiR-126(-/-) HUCBC-treatment abolished the benefits of naive-HUCBC-treatment in T2DM stroke mice. In vitro, knock-in of miR-126 in primary cultured brain endothelial cells (BECs) or treatment of BECs with naive-HUCBCs significantly increased capillary-like tube formation, and increased axonal outgrowth in primary cultured cortical neurons; whereas treatment of BECs or cortical neurons with miR-126(-/-) HUCBC attenuated HUCBC-treatment-induced capillary tube formation and axonal outgrowth. Our data suggest delayed HUCBC-treatment of stroke increases vascular/white-matter remodeling and anti-inflammatory effects; MiR-126 may contribute to HUCBC-induced neurorestorative effects in T2DM mice.
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页码:102 / 113
页数:12
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Cui, Xu
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Cui, Yishen
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Zacharek, Alex
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Roberts, Cynthia
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Liu, Xinfeng
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Nanjing Univ, Sch Med, Jinling Hosp, Nanjing, Jiangsu, Peoples R China Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Dai, Xiangguo
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA

Lu, Mei
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Chopp, Michael
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Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA
Oakland Univ, Rochester, MI 48063 USA Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA