Pouly Julia, Hagège Albert A, Vilquin Jean-Thomas, Bissery Alvine, Rouche Andrée, Bruneval Patrick, Duboc Denis, Desnos Michel, Fiszman Marc, Fromes Yves, Menasché Philippe
INSERM U582, Institute of Myology, Groupe Hospitalier Pitié-Salpétrière, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
Circulation. 2004 Sep 21;110(12):1626-31. doi: 10.1161/01.CIR.0000142861.55862.15. Epub 2004 Sep 13.
The benefits of skeletal myoblast (SM) transplantation on infarcted myocardium have been investigated extensively; however, little is known about its effects in nonischemic cardiomyopathy models. To address this issue, we tested SM transplantation in CHF147 Syrian hamsters, a strain characterized by a delta-sarcoglycan deficiency that phenotypically features the human setting of primary dilated cardiomyopathy.
Cell culture techniques were used to prepare approximately 5x10(6) muscle cells from autologous tibialis anterior muscle, of which 50% were SMs (desmin staining). The cells were injected in 6 sites across the left ventricular wall (n=14). Control animals (n=12) received equivalent volumes of culture medium. Left ventricular systolic function was assessed in a blinded fashion from 2D echocardiographic left ventricular fractional area change, before transplantation, and 4 weeks later. Explanted hearts were processed for the detection of myotubes and quantification of fibrosis. Baseline functional data did not differ between the 2 groups. Four weeks after transplantation, 6 of the 10 surviving grafted hamsters were improved compared with 0 of the 8 survivors of the control group. This translated into a 6% decrease in fractional area change in controls compared with a 24% increase in cell-transplanted hamsters (P=0.001). Engrafted myotubes were consistently detected in all SM transplanted hearts by immunohistochemistry, whereas fibrosis was not worsened by cell injections.
These data suggest that the functional benefits of SM transplantation might extend to nonischemic cardiomyopathy.
骨骼肌成肌细胞（SM）移植对梗死心肌的益处已得到广泛研究；然而，其在非缺血性心肌病模型中的作用却知之甚少。为解决这一问题，我们在CHF147叙利亚仓鼠中测试了SM移植，该品系的特征是δ-肌聚糖缺乏，其表型特征与人类原发性扩张型心肌病相似。
采用细胞培养技术从自体胫前肌制备约5×10⁶个肌肉细胞，其中50%为SM（结蛋白染色）。将这些细胞注射到左心室壁的6个部位（n = 14）。对照组动物（n = 12）接受等量的培养基。在移植前和4周后，以盲法通过二维超声心动图测量左心室面积变化分数来评估左心室收缩功能。取出心脏进行肌管检测和纤维化定量分析。两组的基线功能数据无差异。移植后4周，10只存活的移植仓鼠中有6只功能改善，而对照组的8只存活仓鼠中无改善。这导致对照组的面积变化分数下降6%，而细胞移植的仓鼠增加24%（P = 0.001）。通过免疫组织化学在所有SM移植的心脏中均能持续检测到植入的肌管，且细胞注射并未使纤维化加重。
这些数据表明，SM移植的功能益处可能扩展至非缺血性心肌病。
