AUTOLOGOUS SKELETAL-MYOBLAST-SHEET TRANSPLANTATION IMPROVED PORCINE CARDIAC FUNCTION WITHOUT INCREASING RISK OF ARRHYTHMIA
AUTOLOGOUS SKELETAL-MYOBLAST-SHEET TRANSPLANTATION IMPROVED PORCINE CARDIAC FUNCTION WITHOUT INCREASING RISK OF ARRHYTHMIA
复制标题
自体骨骼成肌细胞片移植可改善猪心脏功能而不增加心律失常风险
DOI：
10.1016/s0735-1097(12)61059-6
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发表时间：
2012
影响因子：
24
通讯作者：
T. Okano
中科院分区：
文献类型：
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作者：
Y. Terajima;Tatsuya Shimizu;S. Tsuruyama;H. Sekine;N. Hagiwara;T. Okano
自体成骨骼肌细胞（SkM）注射已被用于心肌梗死的修复。然而，一些临床试验一直受到室性心动过速的困扰。本研究探讨了SkM薄片移植梗死心肌后猪模型的心电稳定性。方法小型猪经球囊导管封堵LAD 2 h后再灌注。4周后，将12张SkM薄片植入梗死心肌（薄片组n= 8），将等量的SkM细胞注射到心肌（注射组n= 7），并进行假手术（假手术组n= 7）。植入式心电环路记录仪（ILR）在左胸皮下植入。移植后4周，我们用MDCT评估心功能，询问ILR，并进行程序性心室刺激（PVS）。为了评估炎症和损伤反应，分别在移植后1、3、7和30天采用细胞因子阵列法和ELISA法检测炎症因子、高敏CRP和Troponin-I。用抗巨噬细胞免疫化学染色观察炎症反应。结果与注射组和sham组相比，Sheet组患者的心功能得到改善（左室射血分数改变率分别为5.8±2.7,- 1.0±2.6和- 3.8±1.8 %,P < 0.05 (ANOVA)）。各组均未检测到VF，注射组1头猪检测到VT。VF诱导率分别为25.0%、71.4%和28.6%。与Sheet组和sham组比较，注射组血钙素i和IL-6水平升高。薄片组未见细胞向心肌内迁移，但注射组心肌内注射细胞周围可见抗巨噬细胞阳性细胞。结论梗死心肌移植SkM片较注射SkM片改善心功能，但不增加心律失常发生率。心肌炎症可增加心律失常的风险。
BackgroundAutologous skeletal myoblast (SkM) injection has been used for repairing infracted myocardium. However, some clinical trials have been plagued by ventricular tachyarrhythmia. This study is investigated the cardiac electrical stability of porcine model after SkM sheet transplantation in infarcted myocardium.MethodsMale mini-pigs underwent LAD occlusion by a balloon catheter for 2 h, followed by reperfusion. After 4 weeks, 12 SkM sheets were implanted onto infarcted myocardium (Sheet-group n= 8), the same amount of cells were injected into the myocardium (Injection-group n= 7) and sham operations were performed (Sham-group n= 7). Implantable ECG loop recorder (ILR) was implanted subcutaneous on the left thorax. At 4 weeks after the transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS). For assessing the inflammatory and injury response, inflammation factors, and high-sensitive CRP and Troponin-I were measured at 1, 3, 7, and 30 days after the transplantation by cytokine array method and ELISA, respectively. For observing inflammation, the tissues were stained immunochemically with anti-macrophage.ResultsSheet-group improved their cardiac function compared with Injection-group and Sham-group (left ventricular ejection fraction change: 5.8 ± 2.7, − 1.0 ± 2.6 and − 3.8 ± 1.8 % in Sheet, Injection and Sham-groups, respectively, P < 0.05 (ANOVA)). No VF was detected by ILR in all groups, while VT was detected in one pig of Injection-group. The percentage of animals in which VF was induced was 25.0%, 71.4% and 28.6%, respectively. Toroponin-I and IL-6 levels increase in Injection-group compared with Sheet and Sham-groups. Although there are no migrating cells into myocardium in Sheet-group, anti-macrophage positive cells were observed around injected cells in myocardium in Injection-group.ConclusionsSkM sheets transplantation in infarcted myocardium improved cardiac function over SkM Injection without increasing arrhythmogenicity. Myocardium inflammation may increase the arrhythmia risk.