Benabdallah Basma F, Bouchentouf Manaf, Rousseau Joel, Bigey Pascal, Michaud Annick, Chapdelaine Pierre, Scherman Daniel, Tremblay Jacques P
Génétique humaine, Centre de Recherche du CHUL, Québec, Canada.
Cell Transplant. 2008;17(3):337-50. doi: 10.3727/096368908784153913.
Duchenne muscular dystrophy is a recessive disease due to a mutation in the dystrophin gene. Myoblast transplantation permits to introduce the dystrophin gene in dystrophic muscle fibers. However, the success of this approach is reduced by the short duration of the regeneration following the transplantation, which reduces the number of hybrid fibers. Our aim was to verify whether the success of the myoblast transplantation is enhanced by blocking the myostatin signal with an antagonist, follistatin. Three different approaches were studied to overexpress follistatin in the muscles of mdx mice transplanted with myoblasts. First, transgenic follistatin/mdx mice were generated; second, a follistatin plasmid was electroporated in mdx muscles, and finally, follistatin was induced in mdx mice muscles by a treatment with a histone deacetylase inhibitor. The three approaches improved the success of the myoblast transplantation. Moreover, fiber hypertrophy was also observed in all muscles, demonstrating that myostatin inhibition by follistatin is a good method to improve myoblast transplantation and muscle function. Myostatin inhibition by follistatin in combination with myoblast transplantation is thus a promising novel therapeutic approach for the treatment of muscle wasting in diseases such as Duchenne muscular dystrophy.
杜氏肌营养不良症是一种由肌营养不良蛋白基因突变引起的隐性疾病。成肌细胞移植可将肌营养不良蛋白基因导入营养不良的肌纤维中。然而，由于移植后再生持续时间短，这种方法的成功率降低，进而减少了杂种纤维的数量。我们的目的是验证用拮抗剂卵泡抑素阻断肌生成抑制素信号是否能提高成肌细胞移植的成功率。研究了三种不同的方法，以使卵泡抑素在移植了成肌细胞的mdx小鼠肌肉中过表达。首先，培育出转基因卵泡抑素/mdx小鼠；其次，将卵泡抑素质粒电穿孔导入mdx小鼠肌肉；最后，通过用组蛋白脱乙酰酶抑制剂处理，在mdx小鼠肌肉中诱导卵泡抑素表达。这三种方法均提高了成肌细胞移植的成功率。此外，在所有肌肉中还观察到纤维肥大，表明卵泡抑素抑制肌生成抑制素是提高成肌细胞移植和肌肉功能的一种好方法。因此，卵泡抑素抑制肌生成抑制素并联合成肌细胞移植是治疗杜氏肌营养不良症等疾病中肌肉萎缩的一种有前景的新型治疗方法。
