Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Development. 2011 Sep;138(17):3639-46. doi: 10.1242/dev.067595.
Skeletal muscle tissue provides mechanical force for locomotion of all vertebrate animals. It is prone to damage from acute physical trauma and physiological stress. To cope with this, it possesses a tremendous capacity for rapid and effective repair that is widely held to be accomplished by the satellite cells lying between the muscle fiber plasmalemma and the basement membrane. Cell transplantation and lineage-tracing studies have demonstrated that Pax7-expressing (Pax7(+)) satellite cells can repair damaged muscle tissue repeatedly after several bouts of acute injury. These findings provided evidence that Pax7(+) cells are muscle stem cells. However, stem cells from a variety of other origins are also reported to contribute to myofibers upon engraftment into muscles, questioning whether satellite cells are the only stem cell source for muscle regeneration. Here, we have engineered genetic ablation of Pax7(+) cells to test whether there is any significant contribution to muscle regeneration after acute injury from cells other than this source. We find that such elimination of Pax7(+) cells completely blocks regenerative myogenesis either following injury to the tibialis anterior (TA) muscle or after transplantation of extensor digitorum longus (EDL) muscles into nude mice. As Pax7 is specifically expressed in satellite cells, we conclude that they are essential for acute injury-induced muscle regeneration. It remains to be established whether there is any significant role for stem cells of other origins. The implications of our results for muscle stem cell-based therapy are discussed.
骨骼肌组织为所有脊椎动物的运动提供机械力。它容易受到急性物理创伤和生理应激的损伤。为了应对这种情况，它具有巨大的快速和有效修复能力，这种能力被广泛认为是由位于肌纤维质膜和基膜之间的卫星细胞完成的。细胞移植和谱系追踪研究表明，表达 Pax7（Pax7(+)）的卫星细胞可以在几次急性损伤后反复修复受损的肌肉组织。这些发现为 Pax7(+)细胞是肌肉干细胞提供了证据。然而，也有报道称，来自各种其他来源的干细胞在植入肌肉后也有助于肌纤维的形成，这使得人们质疑卫星细胞是否是肌肉再生的唯一干细胞来源。在这里，我们通过基因工程使 Pax7(+)细胞缺失，以测试在急性损伤后，除了这种来源之外，其他细胞对肌肉再生是否有任何显著贡献。我们发现，这种 Pax7(+)细胞的消除完全阻止了前胫骨肌（TA）肌肉损伤或伸趾长肌（EDL）肌肉移植到裸鼠后的再生肌发生。由于 Pax7 特异性表达于卫星细胞，我们得出结论，它们是急性损伤诱导的肌肉再生所必需的。其他来源的干细胞是否有重要作用仍有待确定。我们的研究结果对基于肌肉干细胞的治疗具有重要意义。
