Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy
Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy
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DOI：
10.1016/j.jtcvs.2005.02.024
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发表时间：
2005-09-01
影响因子：
6
通讯作者：
Matsuda, H
中科院分区：
文献类型：
--
作者：
Memon, IA;Sawa, Y;Matsuda, H
目的：用分离的骨骼肌成肌细胞和骨髓单个核细胞进行细胞心脏成形术是治疗心力衰竭的一个令人鼓舞的策略。方法：将自体骨骼肌成肌细胞（1 × 10 ~（8））和自体骨髓单个核细胞（3 × 10 ~（6））直接注射到结扎冠状动脉左前降支2周的犬心肌损伤处，观察成肌细胞和骨髓单个核细胞联合移植治疗犬心肌缺血的效果。处理组如下：骨骼肌成肌细胞加骨髓单核细胞（联合细胞疗法，n = 4）、成肌细胞（n = 4）、骨髓单核细胞（n = 4）和仅培养基（n = 4）。在类似设计的支持实验中，在接受左前降支冠状动脉结扎的大鼠心脏中进行细胞移植后，通过酶联免疫吸附试验评估血管生成因子的表达。结果：细胞植入四周后，超声心动图显示，与对照组相比，联合细胞治疗组的心脏性能更好，左心室扩张减少，射血分数显著提高。其他组（预处理，37.7% +/-1.1%，对比联合细胞治疗，55.4% +/- 8.6%;成肌细胞，47.4% +/- 7.4%;骨髓单核细胞，44.4% +/- 6.7%;仅培养基[对照]，34.4% +/- 5.4%; P <0.05）。在仅接受联合细胞治疗的组中观察到显著高数量的新生血管（联合细胞治疗，45.5 +/- 12 × 10（2）/mm（2）;成肌细胞，26.5 +/- 8 × 10（2）/mm（2）;骨髓单个核细胞，30.7 +/- 15 × 10（2）/mm（2）;仅培养基[对照]，7.1 +/- 1 × 10（2）/mm（2）; P < .05）。免疫染色切片表达骨骼特异性标记肌球蛋白重链，但不表达心脏特异性标记肌钙蛋白T。酶联免疫吸附试验结果显示血管内皮生长因子的表达最高（联合细胞治疗，2.9 +/- 0.7 ng/g组织;成肌细胞，0.24 +/- 0.7 ng/g组织;骨髓单核细胞，1.9 +/- 0.2 ng/g组织;仅培养基[对照]，0.19 +/- 0.004 ng/g组织;结论：联合自体细胞治疗可诱导心肌新生和血管新生，增强心脏功能，减少心脏重构，为临床治疗严重缺血性心肌病提供了一种可行的策略。
Objectives: Cellular cardiornyoplasty with isolated skeletal myoblasts and bone marrow mononuclear cells is an encouraging therapeutic strategy for heart failure. We investicated the achievements accomplished with combined cell therapy of skeletal myoblast and bone marrow mononuclear cell transplantation to the ischemic canine myocardium.Methods: Autologous skeletal myoblasts (1 x 10(8)) and autologous bone marrow mononuclear cells (3 x 10(6)) were injected directly into the damaged myocardium of canine hearts that had undergone 2 weeks of left anterior descending coronary artery ligation. Treatment groups were as follows: skeletal myoblasts plus bone marrow mononuclear cells (combined cell therapy, n = 4), myoblasts (n = 4), bone marrow mononuclear cells (n = 4), and medium only (n = 4). In similarly designed supporting experiments, angiogenic factor expression was evaluated by enzyme-linked immunosorbent assay after cell transplantation in rat hearts that had under-gone left anterior descending coronary artery ligation.Results: Four weeks after cell implantation, echocardiography demonstrated better cardiac performance with reduced left ventricular dilation and significantly improved ejection fraction in the combined cell therapy group compared with that seen in the other groups (pretreatment, 37.7% +/- 1.1%, vs combined cell therapy, 55.4% +/- 8.6%; myoblasts, 47.4% +/- 7.4%; bone marrow mononuclear cells, 44.4% +/- 6.7%; medium only [control], 34.4% +/- 5.4%; P < .05). A significantly high number of neovessels were observed in the group receiving combined cell therapy only (combined cell therapy, 45.5 +/- 12 x 10(2)/mm(2); myoblasts, 26.5 +/- 8 x 10(2)/mm(2); bone marrow mononuclear cells, 30.7 +/- 15 x 10(2)/mm(2); medium only [control], 7.1 +/- 1 x 10(2)/mm(2); P < .05). Immunostained sections expressed the skeletal specific marker myosin heavy chain, although they did not express the cardiac specific marker troponin T. Results of enzyme-linked immunosorbent assay showed the highest expression of vascular endothelial growth factor (combined cell therapy, 2.9 +/- 0.7 ng/g tissue; myoblasts, 0.24 +/- 0.7 ng/g tissue; bone marrow mononuclear cells, 1.9 +/- 0.2 ng/g tissue; medium only [control], 0.19 +/- 0.004 ng/g tissue; P < .05) and hepatocyte growth factor in the combined cell therapy hearts.Conclusions: Combined autolooous cellular therapy induced both myogenesis and 4 angiogenesis with enhancement of cardiac performance and reduction of cardiac remodeling, suggesting a capable strategy for treating severe ischemic cardiomyopathy clinically.