Kowalski Kamil, Archacki Rafał, Archacka Karolina, Stremińska Władysława, Paciorek Anna, Gołąbek Magdalena, Ciemerych Maria A, Brzoska Edyta
Department of Cytology, Faculty of Biology University of Warsaw Warsaw Poland.
Laboratory of Systems Biology, Faculty of Biology University of Warsaw Warsaw Poland.
J Cachexia Sarcopenia Muscle. 2016 Sep;7(4):483-96. doi: 10.1002/jcsm.12092. Epub 2015 Nov 3.
The skeletal muscle has the ability to regenerate after injury. This process is mediated mainly by the muscle specific stem cells, that is, satellite cells. In case of extensive damage or under pathological conditions, such as muscular dystrophy, the process of muscle reconstruction does not occur properly. The aim of our study was to test whether mobilized stem cells, other than satellite cells, could participate in skeletal muscle reconstruction.
Experiments were performed on wild-type mice and mice lacking the functional Pax7 gene, that is, characterized by the very limited satellite cell population. Gastrocnemius mice muscles were injured by cardiotoxin injection, and then the animals were treated by stromal derived factor-1 (Sdf-1) with or without granulocyte-colony stimulating factor (G-CSF) for 4 days. The muscles were subjected to thorough assessment of the tissue regeneration process using histological and in vitro methods, as well as evaluation of myogenic factors' expression at the transcript and protein levels.
Stromal derived factor-1 alone and Sdf-1 in combination with G-CSF significantly improved the regeneration of Pax7-/- skeletal muscles. The Sdf-1 and G-CSF treatment caused an increase in the number of mononucleated cells associated with muscle fibres. Further analysis showed that Sdf-1 and G-CSF treatment led to the rise in the number of CD34+ and Cxcr4+ cells and expression of Cxcr7.
Stromal derived factor-1 and G-CSF stimulated regeneration of the skeletal muscles deficient in satellite cells. We suggest that mobilized CD34+, Cxcr4+, and Cxcr7+ cells can efficiently participate in the skeletal muscle reconstruction and compensate for the lack of satellite cells.
骨骼肌在损伤后具有再生能力。这一过程主要由肌肉特异性干细胞即卫星细胞介导。在广泛损伤或病理条件下，如肌肉萎缩症，肌肉重建过程无法正常发生。我们研究的目的是测试除卫星细胞外的动员干细胞是否能参与骨骼肌重建。
在野生型小鼠和缺乏功能性Pax7基因（即卫星细胞数量非常有限）的小鼠身上进行实验。通过注射心肌毒素损伤小鼠腓肠肌，然后用基质衍生因子-1（Sdf-1）单独或联合粒细胞集落刺激因子（G-CSF）对动物进行4天治疗。使用组织学和体外方法对肌肉的组织再生过程进行全面评估，并在转录和蛋白质水平评估生肌因子的表达。
单独使用基质衍生因子-1以及Sdf-1与G-CSF联合使用均显著改善了Pax7-/-骨骼肌的再生。Sdf-1和G-CSF治疗导致与肌纤维相关的单核细胞数量增加。进一步分析表明，Sdf-1和G-CSF治疗导致CD34+和Cxcr4+细胞数量增加以及Cxcr7表达增加。
基质衍生因子-1和G-CSF刺激了卫星细胞缺陷的骨骼肌的再生。我们认为动员的CD34+、Cxcr4+和Cxcr7+细胞可以有效地参与骨骼肌重建并弥补卫星细胞的缺乏。
