Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice.
Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice.
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DOI：
10.1111/j.1582-4934.2009.00998.x
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发表时间：
2011-07
影响因子：
5.3
通讯作者：
Riazuddin S
中科院分区：
文献类型：
--
作者：
Khan M;Mohsin S;Khan SN;Riazuddin S
心肌梗死是老年人死亡的主要原因之一。间充质干细胞（MSCs）供体的年龄是否影响其修复衰老心脏组织的能力尚不清楚。在本研究中，来自表达绿色荧光蛋白的年轻（2个月）和老年（18个月）C57 BL/6小鼠的MSC具有p16 INK 4 a和β-gal相关衰老的特征。在18个月大的野生型C57 BL/6小鼠中，在梗死区域的边缘移植来自年轻和老年动物的MSC，产生心肌梗死。老年组p16 INK 4a蛋白表达率（21.5%± 1.2%）明显高于青年组（9.2%± 2.8%，P < 0.05）。与年轻细胞相比，在老年MSC中也观察到Matrigel上的管形成能力下降以及胰岛素样生长因子-1、成纤维细胞生长因子（FGF-2）、血管内皮生长因子（VEGF）和肝细胞生长因子（HGF）的下调。移植有年轻MSC的小鼠表现出左心室（LV）收缩和舒张功能的显著改善，如dp/dtmax、dp/dtmin、Pmax所示。如CD 31和平滑肌肌动蛋白（SMA）表达所示，LV纤维化面积的减少伴随着新生血管形成。VEGF、基质细胞衍生因子（SDF-1α）和加塔结合因子4（加塔-4）基因的实时RT-PCR分析进一步证实了年龄对MSC向心脏谱系分化和增强的血管生成的影响。这些研究得出的结论是，骨髓间充质干细胞的修复潜力取决于供体的年龄，衰老梗死心肌的修复需要年轻健康的骨髓间充质干细胞。
Myocardial infarction is one of the leading causes of mortality in aged people. Whether age of donors of mesenchymal stem cells (MSCs) affects its ability to repair the senescent heart tissue is unknown. In the present study, MSCs from young (2 months) and aged (18 months) green fluorescent protein expressing C57BL/6 mice were characterized with p16INK4a and β-gal associated senescence. Myocardial infarction was produced in 18-month-old wild-type C57BL/6 mice transplanted with MSCs from young and aged animals in the border of the infarct region. Expression of p16INK4a in MSCs from aged animals was significantly higher (21.5%± 1.2, P < 0.05) as compared to those from young animals (9.2%± 2.8). A decline in the tube-forming ability on Matrigel was also observed in aged MSCs as well as down-regulation of insulin-like growth factor-1, fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) compared to young cells. Mice transplanted with young MSCs exhibited significant improvement in their left ventricle (LV) systolic and diastolic function as demonstrated by dp/dtmax, dp/dtmin, Pmax. Reduction in the LV fibrotic area was concomitant with neovascularization as demonstrated by CD31 and smooth muscle actin (SMA) expression. Real-time RT-PCR analysis for VEGF, stromal cell derived factor (SDF-1α) and GATA binding factor 4 (GATA-4) genes further confirmed the effect of age on MSC differentiation towards cardiac lineages and enhanced angiogenesis. These studies lead to the conclusion that repair potential of MSCs is dependent on the age of donors and the repair of senescent infarcted myocardium requires young healthy MSCs.
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DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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