G-CSF promotes bone marrow cells to migrate into infarcted mice heart, and differentiate into cardiomyocytes

被引:53
作者
Fukuhara, S
Tomita, S
Nakatani, T
Ohtsu, Y
Ishida, M
Yutani, C
Kitamura, S
机构
[1] Natl Cardiovasc Ctr, Dept Regenerat Med & Tissue Engn, Osaka, Japan
[2] Natl Cardiovasc Ctr, Dept Pathol, Osaka, Japan
[3] Natl Cardiovasc Ctr, Dept Cardiovasc Surg, Osaka, Japan
[4] Natl Cardiovasc Ctr, Dept Organ Transplantat, Osaka, Japan
关键词
bone marrow; stem cells; cardiomyocytes; regeneration; G-CSF;
D O I
10.3727/000000004783983486
中图分类号
Q813 [细胞工程];
学科分类号
摘要
A recent study showed that granulocyte-colony stimulating factor (G-CSF) treatment improved the infarcted cardiac function. Although mobilized stem cells may affect it, the mechanism is unclear. In this study, we investigated the origins of stem cells and phenotypic changes of the migrated cells, and evaluated the efficacy of G-CSF. Eighteen C57BL/6 mice were irradiated (900 cGy) and GFP mouse-derived bone marrow cells (GFP-BMC: 106 cells) were injected via a tail vein followed by splenectomy 4 weeks later. Ligation of the left descending coronary artery was performed 2 weeks later. Recombinant human G-CSF (200 mug/kg/day) was injected for 3 days before and 5 days after ligation (group 1, n = 10). Saline was injected in group 2 (n = 8). Four weeks after infarction, hearts and other organs were fixed for histology. The survival rate after postoperative day 3 in group 1 was 100%, while that in group 2 was 50% (p = 0.03). Bone marrow-derived GFP cells (BMD-GFP) in group 1 (103.3 +/- 71.9/mm(2)) were located at the infarcted border area significantly more than those in group 2 (43.6 +/- 23.7/mm(2)) (p < 0.0001). BMD-GFP cells were positive for troponin 1 (16.6%), myosin heavy chain-slow (16.7%), and nestin (8.8%) in group 1. Ki-67-positive BMD-GFP in group 1 (10.0 +/- 7.0/mm(2)) were significantly more than those in group 2 (4.8 +/- 6.1/mm(2)) (P = 0.01). G-CSF increased the survival rate after infarction. G-CSF promoted BMC to migrate into the infarcted border area. Bone marrow was one of the origins of regenerated cardiomyocytes.
引用
收藏
页码:741 / 748
页数:8
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