Tambara Keiichi, Sakakibara Yutaka, Sakaguchi Genichi, Lu Fanglin, Premaratne Goditha U, Lin Xue, Nishimura Kazunobu, Komeda Masashi
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Circulation. 2003 Sep 9;108 Suppl 1:II259-63. doi: 10.1161/01.cir.0000087430.17543.b8.
It is not clear how many skeletal myoblasts (SM) can survive and exert beneficial effects in the host myocardial infarction (MI) area. We assessed the hypothesis that a large number of SM can replace the MI area with reverse left ventricular (LV) remodeling.
MI was created by left coronary artery ligation in male Lewis rats. Four weeks after ligation, 45 rats had skeletal myoblast transplantation in the MI area. They were randomized into 3 groups according to the number of SM: group I (n=15), 5 x 10(7); group II (n=15), 5 x 10(6); and group III (n=15), 5 x 10(5) cells. Donor SM were obtained from neonatal Lewis rats and directly used without expansion. Another four weeks later, all rats were sacrificed following hemodynamic assessment. All heart sections were stained with anti-fast skeletal myosin heavy chain (FSMHC) antibody to determine the spacial extent of donor myocytes.
Four weeks after transplantation, LV diastolic dimension was decreased, fractional area change was increased, and MI size was decreased maximally in group I. Histological study showed that donor cells positive for FSMHC occupied the MI area with nearly normal wall thickness in group I, in which estimated volume of donor-derived muscle tissue was 40 mm3. In the other groups, FSMHC-positive cells were found only partly in the MI area.
A large number of freshly isolated neonatal SM can survive in the host and fully replace the infarcted myocardium with reverse LV remodeling in rats with MI.
目前尚不清楚有多少骨骼肌成肌细胞（SM）能够在宿主心肌梗死（MI）区域存活并发挥有益作用。我们评估了大量SM能够替代MI区域并逆转左心室（LV）重塑的假说。
通过结扎雄性Lewis大鼠的左冠状动脉制造MI模型。结扎4周后，45只大鼠在MI区域进行骨骼肌成肌细胞移植。根据SM数量将它们随机分为3组：I组（n = 15），5×10⁷个细胞；II组（n = 15），5×10⁶个细胞；III组（n = 15），5×10⁵个细胞。供体SM取自新生Lewis大鼠，未经扩增直接使用。又过了4周后，在进行血流动力学评估后处死所有大鼠。所有心脏切片用抗快速骨骼肌肌球蛋白重链（FSMHC）抗体染色，以确定供体心肌细胞的空间范围。
移植4周后，I组左心室舒张直径减小，面积变化分数增加，MI大小最大程度减小。组织学研究显示，I组中FSMHC阳性的供体细胞占据了MI区域，且壁厚度接近正常，其中估计供体来源的肌肉组织体积为40mm³。在其他组中，仅在MI区域部分发现FSMHC阳性细胞。
大量新鲜分离的新生SM能够在宿主体内存活，并在MI大鼠中完全替代梗死心肌，同时逆转LV重塑。
