Fetal skeletal muscle progenitors have regenerative capacity after intramuscular engraftment in dystrophin deficient mice.
Fetal skeletal muscle progenitors have regenerative capacity after intramuscular engraftment in dystrophin deficient mice.
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DOI：
10.1371/journal.pone.0063016
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sehara-Fujisawa A
中科院分区：
文献类型：
--
作者：
Sakai H;Sato T;Sakurai H;Yamamoto T;Hanaoka K;Montarras D;Sehara-Fujisawa A
肌肉卫星细胞(SCs)是驻留在骨骼肌中的干细胞，有助于肌肉损伤后的再生。干细胞起源于小鼠胚胎发育过程中表达转录因子Pax3和/或Pax7的骨骼肌祖细胞。然而，当这些胎儿祖细胞移植到成年肌肉中时，是否具有再生能力尚不清楚。在这里，我们通过研究从Pax3GFP/+胚胎中分离的胎儿骨骼肌祖细胞(FMP)是否有能力在植入Duchenne肌营养不良症模型的dystrophin缺陷小鼠后再生肌肉来解决这个问题。比较FMPs与成年Pax3GFP/+小鼠来源的SCs在再生肌中植入和进入生肌程序的能力。移植的FMP有助于dystrophin缺陷小鼠受损肌纤维的重建。然而，尽管FMPs和SCs在培养上具有相似的成肌能力，但FMPs在体内的再生能力低于SCs。与MyoD阴性的FMP相比，激活MyoD的FMP植入更有效地再生肌纤维。对这些细胞的转录组和表面标记分析表明，肌源性启动对于有效的肌源性植入非常重要。我们的发现表明，FMPs在肌肉修复和退行性肌肉疾病的细胞治疗方面具有再生能力。
Muscle satellite cells (SCs) are stem cells that reside in skeletal muscles and contribute to regeneration upon muscle injury. SCs arise from skeletal muscle progenitors expressing transcription factors Pax3 and/or Pax7 during embryogenesis in mice. However, it is unclear whether these fetal progenitors possess regenerative ability when transplanted in adult muscle. Here we address this question by investigating whether fetal skeletal muscle progenitors (FMPs) isolated from Pax3GFP/+ embryos have the capacity to regenerate muscle after engraftment into Dystrophin-deficient mice, a model of Duchenne muscular dystrophy. The capacity of FMPs to engraft and enter the myogenic program in regenerating muscle was compared with that of SCs derived from adult Pax3GFP/+ mice. Transplanted FMPs contributed to the reconstitution of damaged myofibers in Dystrophin-deficient mice. However, despite FMPs and SCs having similar myogenic ability in culture, the regenerative ability of FMPs was less than that of SCs in vivo. FMPs that had activated MyoD engrafted more efficiently to regenerate myofibers than MyoD-negative FMPs. Transcriptome and surface marker analyses of these cells suggest the importance of myogenic priming for the efficient myogenic engraftment. Our findings suggest the regenerative capability of FMPs in the context of muscle repair and cell therapy for degenerative muscle disease.