G-CSF treatment increases side population cell infiltration after myocardial infarction in mice
G-CSF treatment increases side population cell infiltration after myocardial infarction in mice
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DOI：
10.1016/j.yjmcc.2004.03.005
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发表时间：
2004-05-01
影响因子：
5
通讯作者：
Saito, Y
中科院分区：
文献类型：
--
作者：
Adachia, Y;Imagawa, J;Saito, Y
粒细胞集落刺激因子（G-CSF）已被报道动员骨髓多能干细胞，心肌梗死（MI）后分化为心肌细胞。然而，还没有任何关于G-CSF对MI部位干细胞浸润的影响的报道。将经历冠状动脉闭塞的小鼠的心脏分离并用胶原酶消化。使用Percoll密度梯度收集心脏中的浸润细胞。使用Hoechst 33342染料分选浸润细胞的侧群（SP）细胞。MI后1 ~ 14 d，心肌内有数百个SP细胞浸润。无梗死心肌SP细胞较少。与载体组相比，在4-d G-CSF处理组中浸润的SP细胞增加（1106 +/-106 vs. 323 +/-26/心脏，P < 0.05）。G-CSF治疗对炎性细胞浸润无影响。在一个单独的系列实验中，我们证实了浸润的SP细胞来自骨髓。也就是说，移植了ROSA 26（β-半乳糖苷酶转基因）小鼠骨髓的小鼠梗死心脏中的SP细胞对β-半乳糖苷酶呈阳性。免疫组化显示心肌梗死后梗死灶内有Sca-1（+）/CD 45（-）细胞存在。因此，SP细胞可以浸润到梗死的心脏。G-CSF增强了这种干细胞浸润，而不增加炎性细胞。这些结果表明，G-CSF可以促进心肌再生，而不加重炎症在梗死心脏。(C)2004 Elsevier Ltd.保留所有权利。
Granulocyte-colony stimulating factor (G-CSF) has been reported to mobilize bone marrow multi-potent stem cells, which differentiate into cardiac myocytes after myocardial infarction (MI). However, there have not been any reports regarding the effect of G-CSF on stem cell infiltration in the MI site. Hearts of mice that had undergone coronary occlusion were isolated and digested with collagenase. Infiltrating cells in the heart were collected using Percoll density gradients. The infiltrating cells were sorted for side population (SP) cells using Hoechst 33342 dye. Hundreds of infiltrating SP cells were found in the heart from 1 to 14 d after MI. There were only a few SP cells in hearts without infarction. Infiltrating SP cells were increased in the 4-d G-CSF treated group compared with the vehicle group (1106 +/- 106 vs. 323 +/- 26/heart, P < 0.05). The infiltration of inflammatory cells was not influenced by the G-CSF treatment. In a separate series of experiments, we confirmed that the infiltrating SP cells were derived from bone marrow. That is, SP cells in the infarcted hearts of mice, which had been transplanted with bone marrow from ROSA 26 (beta-galactosidase transgenic) mice, were positive for beta-galactosidase. In the immunohistochemical examination, Sca-1(+)/CD45(-) cells were existed in the infarcted site after MI. Therefore, SP cells may infiltrate into infarcted heart. G-CSF augmented this kind of stem cell infiltration without increasing inflammatory cells. These results suggest that G-CSF may enhance myocardial regeneration without aggravated inflammation in the infarcted heart. (C) 2004 Elsevier Ltd. All rights reserved.