Long-term engraftment of myogenic progenitors from adipose-derived stem cells and muscle regeneration in dystrophic mice
Long-term engraftment of myogenic progenitors from adipose-derived stem cells and muscle regeneration in dystrophic mice
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脂肪干细胞的肌源性祖细胞的长期植入和营养不良小鼠的肌肉再生
DOI：
10.1093/hmg/ddv316
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发表时间：
2015-11-01
影响因子：
3.5
通讯作者：
Zhang，Cheng
中科院分区：
文献类型：
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作者：
Zhang，Yu;Zhu，Yuling;Zhang，Cheng
干细胞治疗是治疗杜氏肌营养不良症（DMD）的一种很有前途的方法；然而，它的应用受到细胞植入不良的阻碍。迄今为止，还没有报道描述脂肪来源干细胞（ADSCs）有效产生肌源性祖细胞，可以促进肌肉再生。在本研究中，我们用forskolin、碱性成纤维细胞生长因子、糖原合成酶激酶3β抑制剂6-溴靛红素-3′-肟以及ADSC培养的上清液检测了ADSC分化的祖细胞的致瘤潜能。结果表明，肌源性祖细胞的增殖群体可以从ADSCs中获得，这些ADSCs具有与肌肉卫星细胞相似的特征，并且能够最终分化为多核肌管。通过肌内注射或全身递送将祖细胞移植到DMD模型mdxmice中，可成功植入骨骼肌长达12周，产生新的肌纤维，恢复肌营养不良蛋白的表达，并有助于卫星细胞区室。这些发现强调了来源于ADSCs的肌源性祖细胞在肌营养不良治疗中的潜在应用。
Stem cell therapy is a promising approach for treating Duchenne muscular dystrophy (DMD); however, its application is hindered by poor cell engraftment. There have been no reports to date describing the efficient generation of myogenic progenitors from adipose-derived stem cells (ADSCs) that can contribute to muscle regeneration. In this study, we examined thein vivomyogenic potential of progenitors differentiated from ADSCs using forskolin, basic fibroblast growth factor, the glycogen synthase kinase 3β inhibitor 6-bromoindirubin-3′-oxime as well as the supernatant of ADSC cultures. The results indicate that a proliferative population of myogenic progenitors can be derived from ADSCs that have characteristics similar to muscle satellite cells and are capable of terminal differentiation into multinucleated myotubes. When transplanted into DMD modelmdxmice either by intramuscular injection or systemic delivery, progenitors were successfully engrafted in skeletal muscle for up to 12 weeks, and generated new muscle fibers, restored dystrophin expression and contributed to the satellite cell compartment. These findings highlight the potential application of myogenic progenitors derived from ADSCs to the treatment of muscular dystrophy.