Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA.
Shriners Hospital for Children, Galveston, TX, USA.
J Physiol. 2017 Nov 1;595(21):6687-6701. doi: 10.1113/JP274841. Epub 2017 Oct 1.
Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors.
Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7 -DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2'-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P < 0.05). Burn injury induced robust atrophy in muscles located both proximal and distal to the injury site (∼30% decrease in fibre cross-sectional area, P < 0.05). Additionally, burn injury induced skeletal muscle regeneration, satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P < 0.05). These findings support an integral role for satellite cells in the aetiology of lean tissue recovery following a severe burn injury.
严重烧伤会导致显著的骨骼肌消耗，从而阻碍康复。卫星细胞（骨骼肌干细胞）的活性在烧伤损伤后发生改变，可能阻碍肌肉的再生。严重烧伤诱导卫星细胞增殖和融合到肌纤维中，损伤部位近端肌肉的活性更高。在小鼠烫伤烧伤后，条件性耗尽卫星细胞会减弱肌纤维面积和体积的恢复。烧伤后骨骼肌的再生需要卫星细胞的活性，这凸显了卫星细胞在预防烧伤幸存者长期虚弱方面的治疗潜力。
严重烧伤会导致严重的骨骼肌萎缩；持续的肌肉萎缩和虚弱是主要的并发症，会阻碍烧伤康复。烧伤创伤后肌肉质量的丧失有许多因素，我们之前已经在儿科患者的烧伤损伤后观察到肌肉卫星细胞的同时激活和凋亡。为了确定卫星细胞在烧伤后肌肉恢复过程中的必要性，我们使用了一种遗传修饰的小鼠模型（Pax7-DTA），该模型允许在骨骼肌中条件性耗尽卫星细胞。此外，还使用 5-乙炔基-2'-脱氧尿苷来确定卫星细胞的增殖、激活和融合。幼年卫星细胞野生型（SC-WT）和卫星细胞耗尽型（SC-Dep）小鼠（8 周龄）随机分为假手术或烧伤损伤组，包括背部烫伤烧伤，覆盖 30%的总体表面积。在烧伤后 7、14 和 21 天研究后肢和背部肌肉。与 SC-WT 相比，SC-Dep 小鼠的卫星细胞耗竭率超过 93%（P<0.05）。烧伤损伤诱导损伤部位近端和远端的肌肉发生明显萎缩（纤维横截面积减少约 30%，P<0.05）。此外，烧伤损伤还诱导骨骼肌再生、卫星细胞增殖和融合。耗尽卫星细胞会损害烧伤后肌肉纤维横截面积和体积的恢复（P<0.05）。这些发现支持卫星细胞在严重烧伤后瘦组织恢复的发病机制中起重要作用。
