Bhagavati Satyakam, Xu Weimin
Department of Neurology, SUNY Downstate Medical Center, 450 Clarkson Ave, NY 11203, USA.
Biochem Biophys Res Commun. 2005 Jul 29;333(2):644-9. doi: 10.1016/j.bbrc.2005.05.135.
Embryonic stem (ES) cells have great therapeutic potential because of their capacity to proliferate extensively and to form any fully differentiated cell of the body, including skeletal muscle cells. Successful generation of skeletal muscle in vivo, however, requires selective induction of the skeletal muscle lineage in cultures of ES cells and following transplantation, integration of appropriately differentiated skeletal muscle cells with recipient muscle. Duchenne muscular dystrophy (DMD), a severe progressive muscle wasting disease due to a mutation in the dystrophin gene and the mdx mouse, an animal model for DMD, are characterized by the absence of the muscle membrane associated protein, dystrophin. Here, we show that co-culturing mouse ES cells with a preparation from mouse muscle enriched for myogenic stem and precursor cells, followed by injection into mdx mice, results occasionally in the formation of normal, vascularized skeletal muscle derived from the transplanted ES cells. Study of this phenomenon should provide valuable insights into skeletal muscle development in vivo from transplanted ES cells.
胚胎干细胞（ES细胞）具有巨大的治疗潜力，因为它们能够大量增殖并形成身体的任何完全分化细胞，包括骨骼肌细胞。然而，要在体内成功生成骨骼肌，需要在ES细胞培养物中选择性诱导骨骼肌谱系，并在移植后，使适当分化的骨骼肌细胞与受体肌肉整合。杜兴氏肌营养不良症（DMD）是一种由于肌营养不良蛋白基因突变导致的严重进行性肌肉萎缩疾病，而mdx小鼠是DMD的动物模型，其特征是缺乏与肌膜相关的蛋白——肌营养不良蛋白。在这里，我们表明，将小鼠ES细胞与富含生肌干细胞和前体细胞的小鼠肌肉制备物共培养，然后注射到mdx小鼠体内，偶尔会导致形成源自移植ES细胞的正常、血管化骨骼肌。对这一现象的研究应该能为移植ES细胞在体内的骨骼肌发育提供有价值的见解。
