PDF(Pubmed)
Abstract：
For ischemic cardiomyopathy (ICM) with limited therapeutic options, the induction of arteriogenesis has the potential to improve cardiac function through major restoration of blood flow. We hypothesized that transplantation of a Notch signaling-modified mesenchymal stem cell (SB623 cell) patch would induce angiogenesis and arteriogenesis in ischemic lesions, leading to improvement of left ventricular (LV) function in a rat ICM model. Two weeks after the induction of ischemia, SB623 cell patch transplantation into ICM rats (SB group, n = 10) or a sham operation (no-treatment group, n = 10) was performed. The LV ejection fraction was significantly improved at 6 weeks after SB623 cell patch transplantation (P < 0.001). Histological findings revealed that the number of von Willebrand factor (vWF)-positive capillary vessels (P < 0.01) and alpha smooth muscle actin (αSMA)- and vWF-positive arterioles with a diameter greater than 20 µm (P = 0.002) was significantly increased in the SB group, suggesting the induction of angiogenesis and arteriogenesis. Moreover, rat cardiomyocytes treated with SB623 cell patch transplantation showed upregulation of ephrin-B2 (P = 0.03) and EphB4 (P = 0.01) gene expression, indicating arteriogenesis induction. In conclusion, SB623 cell patch transplantation improved LV function by inducing angiogenesis and arteriogenesis in a rat ICM model.
摘要：
对于治疗选择有限的缺血性心肌病（ICM），动脉生成的诱导有可能通过主要的血流恢复来改善心脏功能。我们假设Notch信号修饰的间充质干细胞（SB623细胞）贴片的移植将在缺血性病变中诱导血管生成和动脉生成，导致大鼠ICM模型中左心室（LV）功能的改善。诱导缺血两周后，SB623细胞补片移植入ICM大鼠(SB组,n=10）或假手术（无治疗组，进行n=10)。SB623细胞补片移植后6周LV射血分数显著提高(P<0.001)。组织学发现，vonWillebrand因子（vWF）阳性毛细血管（P<0.01）和直径大于20µm的α平滑肌肌动蛋白（αSMA）和vWF阳性小动脉（P=0.002）的数量显着增加SB组，提示血管生成和动脉生成的诱导。此外，SB623细胞补片移植大鼠心肌细胞显示ephrin-B2(P=0.03)和EphB4(P=0.01)基因表达上调,指示动脉生成诱导。总之,SB623细胞补片移植通过诱导大鼠ICM模型中的血管生成和动脉生成来改善LV功能。
