Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.
Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.
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DOI：
10.1097/tp.0000000000001014
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发表时间：
2016-02
期刊：
影响因子：
6.2
通讯作者：
Sawa Y
中科院分区：
文献类型：
--
作者：
Shirasaka T;Miyagawa S;Fukushima S;Kawaguchi N;Nakatani S;Daimon T;Okita Y;Sawa Y
改善收缩和舒张功能可能是治疗心力衰竭的最重要因素。在这项研究中，我们假设细胞片移植可以改善受损心脏的这些功能。我们通过240次/分的连续心室起搏建立了比格犬扩张型心肌病模型。4周后，比格犬接受骨骼肌成肌细胞片移植（SMCST）或假手术，并继续快速心室起搏4周。6只接受SMCST治疗的e8比格犬在手术后4周仍存活。我们通过比较SMCST治疗的比格犬与接受假手术的比格犬（对照组，n = 5）来评估SMCST的心脏效应。与假手术组相比，SMCST组的舒张功能和收缩功能显著改善（对照组vs SMCST组，中位数[四分位数间距]：E/E '，16 [0.9] vs 11 [1.0]; P < 0.001; tau，47 [6.0] vs 36 [4.4] ms：P = 0.005）。射血分数，22（6.0）对46（7.5）%，P < 0.001;收缩末期弹性，2.5（0.4）对8.2（3.5）mm Hg/ml，P = 0.001）。组织学检查显示，对照组心肌中I型胶原的体积和I/III型胶原的比率显著高于SMCST组（I型胶原，6.0 [0.8] vs 2.6 [1.3]; P = 0.006; I/III型胶原的比率，4.8 [1.7] vs 1.2 [0.4]; P = 0.010）。SMCST改善收缩和舒张性能的潜力已得到证实。SMCST可能是扩张型心肌病心脏常规药物治疗的替代疗法。
Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010). The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart.