Novel Model of Tendon Regeneration Reveals Distinct Cell Mechanisms Underlying Regenerative and Fibrotic Tendon Healing.
Novel Model of Tendon Regeneration Reveals Distinct Cell Mechanisms Underlying Regenerative and Fibrotic Tendon Healing.
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DOI：
10.1038/srep45238
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发表时间：
2017-03-23
影响因子：
4.6
通讯作者：
Huang AH
中科院分区：
文献类型：
--
作者：
Howell K;Chien C;Bell R;Laudier D;Tufa SF;Keene DR;Andarawis-Puri N;Huang AH
迄今为止，调控肌腱愈合的细胞和分子机制还知之甚少。在这里，我们用新生小鼠建立了一种新的肌腱再生模型，并表明新生儿通过形成新肌腱来愈合，这种新肌腱沿着肌腱特定的谱系分化，步态和机械性能得到功能性恢复。相比之下，成年人通过纤维血管疤痕愈合，向软骨和骨的异常分化，功能持续受损。谱系追踪发现，SCX谱系细胞的内在招募是新生儿愈合的关键细胞机制，这在成年人中是不存在的。取而代之的是，成体的SCX系腱细胞没有被招募到缺损处，而是转化为异位软骨；在没有腱形成细胞的情况下，外源性αSMA表达的细胞持续形成永久的瘢痕。总而言之，这些结果建立了一个令人兴奋的肌腱再生模型，并揭示了再生肌腱愈合与非再生肌腱愈合之间的新的细胞机制。
To date, the cell and molecular mechanisms regulating tendon healing are poorly understood. Here, we establish a novel model of tendon regeneration using neonatal mice and show that neonates heal via formation of a ‘neo-tendon’ that differentiates along the tendon specific lineage with functional restoration of gait and mechanical properties. In contrast, adults heal via fibrovascular scar, aberrant differentiation toward cartilage and bone, with persistently impaired function. Lineage tracing identified intrinsic recruitment of Scx-lineage cells as a key cellular mechanism of neonatal healing that is absent in adults. Instead, adult Scx-lineage tenocytes are not recruited into the defect but transdifferentiate into ectopic cartilage; in the absence of tenogenic cells, extrinsic αSMA-expressing cells persist to form a permanent scar. Collectively, these results establish an exciting model of tendon regeneration and uncover a novel cellular mechanism underlying regenerative vs non-regenerative tendon healing.