Human ES- and iPS-derived myogenic progenitors restore DYSTROPHIN and improve contractility upon transplantation in dystrophic mice.
Human ES- and iPS-derived myogenic progenitors restore DYSTROPHIN and improve contractility upon transplantation in dystrophic mice.
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DOI：
10.1016/j.stem.2012.02.015
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发表时间：
2012-05-04
期刊：
影响因子：
23.9
通讯作者：
Perlingeiro, Rita C. R.
中科院分区：
文献类型：
--
作者：
Darabi, Radbod;Arpke, Robert W.;Irion, Stefan;Dimos, John T.;Grskovic, Marica;Kyba, Michael;Perlingeiro, Rita C. R.
应用基于细胞的疗法治疗神经肌肉疾病的一个主要障碍是获得适当数量的干细胞/祖细胞以产生有效的植入。使用胚胎干细胞（ES）或诱导多能干细胞（iPS）可以克服这一障碍。然而，迄今为止，还没有实现从人多能细胞衍生出可以恢复肌肉功能的可移植骨骼肌前体。在这里，我们应用Pax 7在人ES/iPS细胞中的条件表达，成功地衍生出大量的肌源性前体，其在移植到营养不良的肌肉中时，能够有效地植入，产生丰富的人源性肌营养不良蛋白阳性肌纤维，其表现出上级强度。重要的是，移植的细胞也会在肌肉卫星细胞区室中播种，并且移植后11个月内存在植入。这项研究提供了从人ES/iPS细胞中衍生功能性骨骼肌源性祖细胞的原理证明，并强调了其在肌营养不良症未来治疗应用中的潜力。
A major obstacle in the application of cell-based therapies for the treatment of neuromuscular disorders is obtaining the appropriate number of stem/progenitor cells to produce effective engraftment. The use of embryonic stem (ES) or induced pluripotent stem (iPS) cells could overcome this hurdle. However to date, derivation of engraftable skeletal muscle precursors that can restore muscle function from human pluripotent cells has not been achieved. Here we applied conditional expression of Pax7 in human ES/iPS cells to successfully derive large quantities of myogenic precursors, which upon transplantation into dystrophic muscle, are able to engraft efficiently, producing abundant human-derived dystrophin-positive myofibers that exhibit superior strength. Importantly, transplanted cells also seed the muscle satellite cell compartment and engraftment is present over 11 months post-transplant. This study provides the proof-of-principle for the derivation of functional skeletal myogenic progenitors from human ES/iPS cells, and highlights their potential for future therapeutic application in muscular dystrophies.
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