背景:目前,Duchenne 型肌营养不良症尚无有效治疗方法,之前的研究表明基因治疗和干细胞移植治疗是可能的"治愈"方法.实验拟将两者结合起来,在动物模型上观察其疗效,并验证之前提出的神经肌肉再生单位的假说.目的:探讨脂肪干细胞移植治疗 Duchenne 型肌营养不良症的有效性和可行性,观察细胞移植对肌纤维、新生血管及神经末梢的影响.方法:体外分离培养mdx鼠脂肪干细胞,经杆状病毒基因载体进行基因修饰,用于移植治疗Duchenne型肌营养不良症模型鼠.移植后检测实验动物的血清肌酸激酶水平、肌肉病理改变及肌肉内dystrophin表达;免疫荧光检测细胞移植后血管、肌肉和神经再生情况.结果与结论:细胞移植后,能够重建模型鼠的dystrophin表达,一定程度上减轻并逆转肌肉的病理损害,进而降低血清激酸激酶水平;此外,细胞移植后能够形成干细胞来源的肌纤维、血管内皮细胞和神经末梢.这些证据表明,脂肪干细胞移植是有希望治疗Duchenne型肌营养不良症的方法之一.
BACKGROUND:Currently, there is no effective treatment for Duchenne muscular dystrophy. Previous studies have shown that gene therapy and stem cel transplantation therapy are possible to be "cure" approaches. Therefore, this study intended to evaluate their efficacy in animal models, and to verify the hypothesis of neuromuscular regeneration unit. OBJECTIVE: To explore the efficacy and feasibility of adipose stem cel transplantation for Duchenne muscular dystrophy and to observe the effects of cel transplantation on muscle fibers, new vessels and nerve endings. METHODS:Adipose stem cels from mdx mice were isolated and cultured in vitro, and then modified by recombinant baculovirus folowed by implantation into mouse models of Duchenne muscular dystrophy. Serum creatine kinase level, muscle pathological changes and muscle dystrophin expression were detected in experimental animals after transplantation; immunofluorescence staining was used to detect vascular, muscle and nerve regeneration after cel transplantation. RESULTS AND CONCLUSION: After transplantation, dystrophin expression was found that could reduce and even reverse the pathological damage of muscles to a certain extent, thereby to reduce the serum level of creatine kinase. In addition, stem cels-derived muscle fiber, vasular endothelial cels and nerve ending were formed after cel transplantation. These evidences domenstrate that adipose stem cel transplantation is one of promising treatments for Duchenne muscular dystrophy.
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