Nishiyama Takashi, Takeda Shin'ichi
Department of Molecular Therapy, National Institute of Neuroscience, Tokyo, Japan.
Brain Nerve. 2012 Jan;64(1):39-46.
Duchenne muscular dystrophy (DMD) is a devastating muscle disorder caused by mutations in the dystrophin gene. There is currently no effective treatment for DMD. Muscle satellite cells are tissue-specific stem cells found in the skeletal muscle; these cells play a central role in postnatal muscle growth and regeneration, and are, therefore, a potential source for stem cell therapy for DMD. However, transplantation of satellite cell-derived myoblasts has not yet been successful in humans. Patient-specific induced pluripotent stem (iPS) cells are expected to be a source for autologous cell transplantation therapy for DMD, because iPS cells can proliferate vigorously in vitro and can differentiate into multiple cell lineages both in vitro and in vivo. Here, we discuss the strategies to generate muscle stem cells from iPS cells. So far, the most promising method for generating muscle stem cells from iPS cells is the conditional overexpression of Pax3 or Pax7 in the differentiating mouse embryoid bodies. However, induction methods for human iPS cells have not yet been developed. Thus, iPS cells are expected to serve as an in vitro disease model system, which will enable us to determine the pathology of muscle diseases and develop pharmaceutical treatments.
杜兴氏肌肉营养不良症（DMD）是一种由肌营养不良蛋白基因突变引起的毁灭性肌肉疾病。目前尚无针对DMD的有效治疗方法。肌肉卫星细胞是在骨骼肌中发现的组织特异性干细胞；这些细胞在出生后肌肉生长和再生中起核心作用，因此是DMD干细胞治疗的潜在来源。然而，卫星细胞来源的成肌细胞移植在人类中尚未成功。患者特异性诱导多能干细胞（iPS细胞）有望成为DMD自体细胞移植治疗的来源，因为iPS细胞可以在体外大量增殖，并且在体外和体内都能分化为多种细胞谱系。在此，我们讨论从iPS细胞生成肌肉干细胞的策略。到目前为止，从iPS细胞生成肌肉干细胞最有前景的方法是在分化的小鼠胚胎体中条件性过表达Pax3或Pax7。然而，人类iPS细胞的诱导方法尚未开发出来。因此，iPS细胞有望作为一种体外疾病模型系统，这将使我们能够确定肌肉疾病的病理并开发药物治疗方法。
