Sato Daisuke, Otani Hajime, Fujita Masanori, Shimazu Takayuki, Yoshioka Kei, Enoki Chiharu, Minato Naoki, Iwasaka Toshiji
Second Department of Internal Medicine;
Exp Clin Cardiol. 2012 Sep;17(3):83-8.
Despite the potential benefit of granulocyte colony-stimulating factor (G-CSF) therapy in patients with acute myocardial infarction (MI), the efficacy of G-CSF in regenerating the heart after MI remains controversial. The authors hypothesize that the limited efficacy of G-CSF is related to its inhibitory effect on recruitment of bone marrow-derived cells (BMCs) to the infarcted tissue. MI was induced in rats with intrabone marrow-bone marrow transplantation from syngenic rats expressing green fluorescence protein to track BMCs. G-CSF was administered for five days after the onset of MI. G-CSF increased the number of CD45(+) cells in the peripheral circulation but did not increase their recruitment to the heart. G-CSF had no effect on myocardial stromal-derived factor-1 alpha and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in mononuclear cells in the peripheral blood and CXCR4(+) cells in the heart. G-CSF had no effect on angiogenesis, myocardial fibrosis or left ventricular function four weeks after MI. These results suggest that G-CSF mobilizes BMCs to the peripheral circulation but does not increase recruitment to the infarcted myocardium despite preservation of the stromal-derived factor-1 alpha/CXCR4 axis.
尽管粒细胞集落刺激因子(G-CSF)疗法对急性心肌梗死(MI)患者具有潜在益处,但G-CSF在MI后心脏再生中的疗效仍存在争议。作者推测,G-CSF疗效有限与其对骨髓源性细胞(BMCs)募集至梗死组织的抑制作用有关。通过将表达绿色荧光蛋白的同基因大鼠进行骨髓内骨髓移植,在大鼠中诱导MI以追踪BMCs。MI发作后给予G-CSF五天。G-CSF增加了外周循环中CD45(+)细胞的数量,但并未增加其向心脏的募集。G-CSF对外周血单核细胞中的心肌基质衍生因子-1α和趋化因子(C-X-C基序)受体4(CXCR4)表达以及心脏中的CXCR4(+)细胞没有影响。MI四周后,G-CSF对血管生成、心肌纤维化或左心室功能没有影响。这些结果表明,G-CSF可将BMCs动员至外周循环,但尽管保留了基质衍生因子-1α/CXCR4轴,却并未增加其向梗死心肌的募集。