Incorporation of macrophages into engineered skeletal muscle enables enhanced muscle regeneration
Incorporation of macrophages into engineered skeletal muscle enables enhanced muscle regeneration
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DOI：
10.1038/s41551-018-0290-2
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发表时间：
2018-12-01
影响因子：
28.1
通讯作者：
Bursac, Nenad
中科院分区：
文献类型：
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作者：
Juhas, Mark;Abutaleb, Nadia;Bursac, Nenad
由于肌肉卫星细胞和免疫系统之间的协同作用，成人骨骼肌具有强大的自我修复能力。肌肉自我修复的体外模型将有助于对肌肉再生的基本认识和肌肉疾病治疗方法的筛选。在这里，我们表明巨噬细胞结合到成年大鼠肌原细胞工程肌肉组织中，可以在体外实现心脏毒性损伤后近乎完整的结构和功能修复。首先，我们表明，与受伤的新生儿来源的工程肌肉相比，成人来源的工程肌肉在受伤后不能适当地自我修复，即使用促再生细胞因子治疗。我们随后发现，在体外工程组织中存在的大鼠骨髓源性巨噬细胞或人血液源性巨噬细胞刺激肌肉卫星细胞介导的肌肉发生，同时显著限制肌纤维凋亡和变性。此外，移植到小鼠背窗室模型的工程组织中骨髓来源的巨噬细胞增强了血管生长、细胞存活、肌肉再生和收缩功能。
Adult skeletal muscle has a robust capacity for self-repair, owing to synergies between muscle satellite cells and the immune system. In vitro models of muscle self-repair would facilitate the basic understanding of muscle regeneration and the screening of therapies for muscle disease. Here, we show that the incorporation of macrophages into muscle tissues engineered from adult-rat myogenic cells enables near-complete structural and functional repair after cardiotoxic injury in vitro. First, we show that-in contrast with injured neonatal-derived engineered muscle-adult-derived engineered muscle fails to properly self-repair after injury, even when treated with pro-regenerative cytokines. We then show that rat bone-marrow-derived macrophages or human blood-derived macrophages resident within the in vitro engineered tissues stimulate muscle satellite cell-mediated myogenesis while significantly limiting myofibre apoptosis and degeneration. Moreover, bone-marrow-derived macrophages within engineered tissues implanted in a mouse dorsal window-chamber model augmented blood vessel ingrowth, cell survival, muscle regeneration and contractile function.