Kanemitsu Naoki, Tambara Keiichi, Premaratne Goditha Upul, Kimura Yu, Tomita Shinji, Kawamura Teruhisa, Hasegawa Koji, Tabata Yasuhiko, Komeda Masashi
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J Heart Lung Transplant. 2006 Oct;25(10):1253-62. doi: 10.1016/j.healun.2006.05.012. Epub 2006 Sep 7.
Myoblast transplantation (Tx) is promising for the improvement of cardiac function in ischemic cardiomyopathy. Insulin-like growth factor-1 (IGF-1) has anti-apoptotic and angiogenic effects, and induces myocyte hypertrophy. Our hypothesis is that topical and slow-release IGF-1 enhances the efficacy of Tx through its multiple functions.
Four weeks after coronary artery ligation, Lewis rats were divided into four groups: (1) IGF-1+Tx, injection of 6 x 10(6) myoblasts into the infarcted area with placement of an IGF-1-impregnated sheet on the left ventricular (LV) free wall; (2) Tx, Tx alone; (3) IGF-1, IGF-1 sheet alone; and (4) control. We measured cardiac function and performed immunohistochemical examinations.
At 4 weeks after treatment, LV diastolic dimension was the smallest, end-systolic elastance was the highest, and tau was the smallest in the IGF-1+Tx group. The graft volume in the IGF-1+Tx group was 3-fold larger than in the Tx group. One day after transplantation, TUNEL-positive donor cells were fewer in the IGF-1+Tx than in the Tx group. Western blot analysis demonstrated that the phosphorylation of Akt increased and the expression of Bax decreased in the transplanted area of IGF-1+Tx rats compared with Tx rats. The vascular density in the peri-infarcted area was larger in IGF-1+Tx than in Tx rats. The mean diameter of graft-derived myotubes was larger in IGF-1+Tx than in Tx animals.
IGF-1 increases the graft volume and enhances the efficacy of Tx in the chronic myocardial infarction model due to its multiple effects of preventing apoptosis, inducing angiogenesis, and promoting myoblast growth.
成肌细胞移植有望改善缺血性心肌病患者的心脏功能。胰岛素样生长因子-1（IGF-1）具有抗凋亡和促血管生成作用，并能诱导心肌细胞肥大。我们的假设是，局部缓释IGF-1通过其多种功能增强了成肌细胞移植的疗效。
冠状动脉结扎4周后，将Lewis大鼠分为4组：（1）IGF-1+移植组，将6×10⁶个成肌细胞注射到梗死区域，并在左心室游离壁放置IGF-1浸渍片；（2）移植组，单纯成肌细胞移植；（3）IGF-1组，单纯IGF-1片；（4）对照组。我们测量了心脏功能并进行了免疫组织化学检查。
治疗4周后，IGF-1+移植组的左心室舒张末期内径最小，收缩末期弹性最高，心肌松弛时间常数最小。IGF-1+移植组的移植体积比移植组大3倍。移植后1天，IGF-1+移植组的TUNEL阳性供体细胞比移植组少。蛋白质免疫印迹分析表明，与移植组大鼠相比，IGF-1+移植组大鼠移植区域内Akt的磷酸化增加，Bax的表达减少。IGF-1+移植组梗死周边区域的血管密度大于移植组大鼠。IGF-1+移植组移植来源的肌管平均直径大于移植组动物。
由于IGF-1具有防止细胞凋亡、诱导血管生成和促进成肌细胞生长的多种作用，它增加了移植体积并增强了慢性心肌梗死模型中成肌细胞移植的疗效。
