生长因子可促进自体骨髓间充质干细胞移植治疗急性心肌梗死

背景：生长因子是干细胞强有力的动员剂，可以增加注射细胞的黏附力和增殖力，诱导干细胞向梗死区迁移、增殖分化，参与心肌修复。 目的：观察肝细胞生长因子和胰岛素样生长因子的联合应用在骨髓间充质干细胞自体移植治疗心肌梗死中的作用。 方法：分离培养兔骨髓间充质干细胞，原代培养后采用红光荧光染料 CM-Dil 标记。结扎冠脉前降支制作兔急性心肌梗死模型，然后随机均分为对照组、骨髓间充质干细胞组、肝细胞生长因子＋胰岛素样生长因子组和肝细胞生长因子＋胰岛素样生长因子＋骨髓间充质干细胞组。于心肌梗死区心肌内分4点共注射不同干预试剂。Masson三色法染色检测存活心肌；免疫荧光检测骨髓间充质干细胞分化；心脏超声评价心功能。 结果与结论：建模后4周，肝细胞生长因子＋胰岛素样生长因子＋骨髓间充质干细胞组 CM-Dil/cTNT＋细胞数量明显多于骨髓间充质干细胞组，其存活心肌最多，左室射血分数改善最明显，左室舒张末径最小。肝细胞生长因子和胰岛素样生长因子联合应用促进自体移植的骨髓间充质干细胞向心肌细胞分化，增加存活心肌数量，改善心功能，抑制心室重构，可能成为心肌梗死后细胞治疗的有效方法。

Growth factors promote the therapeutical effects of autologous bone marrow mesenchymal stem cell transplantation on acute myocardial infarction

BACKGROUND：The growth factor is a potent mobilization agent for stem cels, which can increase adhesion and proliferation of injected cels, induce stem cels to migrate to the infarct zone, proliferate, differentiate, as wel as participate in myocardiac repair.
OBJECTIVE： To investigate the effect of hepatocyte growth factor （HGF） and insulin-like growth factor （IGF） on transplantation of bone marrow mesenchymal stem cels （BMSCs） after acute myocardial infarction.
METHODS： Primary rabbit BMSCs were culturedin vitro and labeled by red fluorescence dye CM-Dil for transplantation. After the mid third of left anterior descending was ligated, model rabbits were grouped into four groups： control group, BMSCs group, HGF＋IGF group, and HGF＋IGF＋BMSCs group （n=6 in each group）. Different interventional agents were injected into the myocardium at four sites within the ischemic region. Masson trichrome staining was performed to determine viable myocardium, and immunofluorescence staining was used to identify BMSCs differentiation. The cardiac function was assessed with Doppler echocardiography.
RESULTS AND CONCLUSION：Four weeks after treatment, CM-Dil/cTNT＋ cels significantly increased in the HGF＋IGF＋BMSCs group, compared with BMSCs group. Consequently, viable myocardial tissues significantly increased, left ventricular ejection fraction was significantly improved, and left ventricular end-diatolic volume significantly decreased in the HGF＋IGF＋BMSCs group, relative to the other three groups. Combination of HGF and IGF that promotes differentiation of transplanted autologous BMSCs into cardiomyocytes, thus increasing viable myocardium, improving left ventricular function, and inhibiting left ventricular remodeling, may be a new method for the celltreatment of acute myocardial infarction.