Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing-induced canine heart failure model
Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing-induced canine heart failure model
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DOI：
10.1016/j.jtcvs.2006.01.024
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发表时间：
2006-10-01
影响因子：
6
通讯作者：
Sawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Hata, Hiroki;Matsumiya, Goro;Sawa, Yoshiki
目标：为了克服与心肌内注射细胞相关的问题，包括细胞损失和有限的移植面积，我们开发了一种细胞递送系统，该系统使用组织工程化成肌细胞移植物生长为片状。在这里，我们评估了我们的方法在犬扩张型心肌病model.Methods的可行性和有效性：Skeleton成肌细胞温育的温度响应培养皿中，并通过降低温度的细胞片脱离。12只犬以230次/min连续心室起搏4周后，将成肌细胞片移植于左室壁（n = 5）或假手术（n = 7）。细胞数量调整为1.5个，相当于每个移植物2.5 × 10（6）个细胞，每只狗接受大约20个移植物。结果：细胞片很容易移植到大面积的左心室表面，没有严重的后遗症。移植物植入4周后，超声心动图显示左心室射血分数（移植物，26.0% +/- 5.6%;对照，19.5% +/- 6.8%; P = 0.05）和短缩分数（移植物，17.9% +/- 3.6%;对照，7.8% +/- 2.1%; P <0.05）显著改善，左心室扩张减少（移植物，7.3 +/- 1.3 cm（2）;对照，10.2 +/- 0.4 cm（2）; P <0.05）和增加的壁厚度（移植物，5.6 +/- 0.7 mm;对照，4.4 +/- 0.6 mm; P <0.05）。组织学证据表明，移植成肌细胞存活，伴随着纤维化和凋亡的显着减少，并显着增加proliferation.Conclusions：骨骼肌成肌细胞片移植衰减心脏重塑和改善心脏性能。这种新方法在大型动物模型中是可行和有效的，这表明了一种治疗终末期扩张型心肌病患者的创新和有前途的策略。
Objective: To overcome problems related to the intramyocardial injection of cells, including cell loss and a limited graft area, we developed a cell delivery system that uses tissue-engineered myoblast grafts grown as sheets. Here, we assessed the feasibility and efficacy of our method in a canine dilated cardiomyopathy model.Methods: Skeletal myoblasts were incubated on temperature-responsive culture dishes, and the sheets of cells were detached by decreasing the temperature. Twelve dogs were given continuous ventricular pacing at 230 beats/min for 4 weeks; then the myoblast sheets (n = 5) were grafted onto the left ventricular wall or a sham operation was performed (n = 7). The number of cells was adjusted to 1.5 similar to 2.5 x 10(6) cells per graft, and each dog received approximately 20 grafts.Results: The cell sheets were easily grafted onto a large area of the left ventricular surface, and there were no serious sequelae. Four weeks after graft implantation, echocardiography demonstrated that the left ventricular ejection fraction (graft, 26.0% +/- 5.6%; control, 19.5% +/- 6.8%; P = .05) and fractional shortening (graft, 17.9% +/- 3.6%; control, 7.8% +/- 2.1%; P < .05) were significantly ameliorated with reduced left ventricular dilatation ( graft, 7.3 +/- 1.3 cm(2); control, 10.2 +/- 0.4 cm(2); P < .05) and increased wall thickness (graft, 5.6 +/- 0.7 mm; control, 4.4 +/- 0.6 mm; P < .05). Histologic evidence indicated the grafted myoblasts had survived, accompanied by a significant reduction in fibrosis and apoptosis, and a significant increase in proliferation.Conclusions: Grafting of skeletal myoblast sheets attenuated cardiac remodeling and improved cardiac performance. This novel method was feasible and effective in a large animal model, suggesting an innovative and promising strategy for treating patients with end-stage dilated cardiomyopathy.