Lillehei Heart Institute, Department of Medicine, University of Minnesota, 4-124 Nils Hasselmo Hall, 312 Church St. S.E., Minneapolis, 55455 MN, USA.
Stem Cell Rev Rep. 2011 Nov;7(4):948-57. doi: 10.1007/s12015-011-9258-2.
Direct reprogramming of adult fibroblasts to a pluripotent state has opened new possibilities for the generation of patient- and disease-specific stem cells. However the ability of induced pluripotent stem (iPS) cells to generate tissue that mediates functional repair has been demonstrated in very few animal models of disease to date. Here we present the proof of principle that iPS cells may be used effectively for the treatment of muscle disorders. We combine the generation of iPS cells with conditional expression of Pax7, a robust approach to derive myogenic progenitors. Transplantation of Pax7-induced iPS-derived myogenic progenitors into dystrophic mice results in extensive engraftment, which is accompanied by improved contractility of treated muscles. These findings demonstrate the myogenic regenerative potential of iPS cells and provide rationale for their future therapeutic application for muscular dystrophies.
直接将成纤维细胞重编程为多能状态为生成患者特异性和疾病特异性干细胞开辟了新的可能性。然而，迄今为止，只有在极少数疾病的动物模型中证明了诱导多能干细胞（iPS 细胞）能够生成介导功能修复的组织。在这里，我们提出了一个原理证明，即 iPS 细胞可有效地用于肌肉疾病的治疗。我们将 iPS 细胞的生成与 Pax7 的条件表达相结合，这是一种强大的方法，可以衍生出成肌祖细胞。将 Pax7 诱导的 iPS 细胞衍生的成肌祖细胞移植到肌肉萎缩症小鼠中会导致广泛的植入，同时伴有治疗肌肉的收缩力提高。这些发现证明了 iPS 细胞的成肌再生潜力，并为其未来在肌肉萎缩症等疾病中的治疗应用提供了依据。
