Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.
Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.
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DOI：
10.1002/jor.23453
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发表时间：
2017-08
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影响因子：
--
通讯作者：
Engler AJ
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文献类型：
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作者：
Thomas KA;Gibbons MC;Lane JG;Singh A;Ward SR;Engler AJ
全层肩袖肌腱（RCT）撕裂对RC肌肉萎缩和脂肪浸润有长期影响，即使在手术肌腱修复后也会造成持久损伤。骨骼肌祖细胞（SMPs）对于肌肉损伤后的修复至关重要，但RC肌肉无法从慢性RCT撕裂中恢复表明修复机制可能存在缺陷。在这里，我们研究了肌肉损伤状态是否是人SMP体外扩增和分化过程中的关键因素。从无、部分层（PT）或全层（FT）RCT撕裂患者的肌肉中分离SMP。尽管使用生长因子，生理生态位刚度，和肌肉模拟细胞外基质（ECM）蛋白，我们发现，从人RC肌肉与RCT撕裂分离的SMPs增殖较慢，但融合成肌球蛋白重链（MHC）阳性肌管的速率高于未撕裂RCT的SMPs。RC肌肉组织的蛋白质组学分析揭示了肌肉组成与病理学的变化，因为与没有撕裂的RC肌肉相比，来自大量RCT撕裂的肌肉的ECM沉积增加。总之，这些数据意味着，在撕裂的RCT的重塑龛素的SMPs的扩展，但分化，从而限制了长期的自我更新必要的手术修复后的再生。
Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair.