Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo.
Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo.
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纯化外切体产品对肩袖肌腱-骨愈合的影响。
DOI：
10.1016/j.biomaterials.2021.121019
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发表时间：
2021-09
期刊：
影响因子：
14
通讯作者：
中科院分区：
文献类型：
--
作者：
外泌体具有多种治疗靶点，但对肌腱套撕裂（RCT）愈合的影响尚不清楚。纯化外泌体产物（PEP）作为一种循环外泌体，具有改善RCT生物力学性能的潜力。在这里，我们建立了一种简单有效的方法，通过体外共培养模型确定PEP在细胞-细胞相互作用中的功能和潜在机制。在体内试验中，成年雌性Sprague-Dawley大鼠接受单侧手术切除并修复冈上肌腱至其插入部位，无论是否使用PEP。PEP促进了成骨细胞和腱细胞的迁移和融合，特别是在细胞间直接接触时。体外和体内RCT模型中潜在基因的表达与生物力学测试和半定量组织学评分一致，表明PEP促进了RC的强度和愈合。我们的观察结果表明，循环外泌体提供了一种有效的选择，以提高手术修复后RCT的愈合速度。PEP治疗后的端部再生似乎与直接细胞-细胞接触和PEP活性之间的相互加强关系有关，表明愈合过程有双重途径。
Exosomes have multiple therapeutic targets, but the effects on healing rotator cuff tear (RCT) remain unclear. As a circulating exosome, purified exosome product (PEP) has the potential to lead to biomechanical improvement in RCT. Here, we have established a simple and efficient approach that identifies the function and underlying mechanisms of PEP on cell-cell interaction using a co-culture model in vitro. In the in vivo trial, adult female Sprague-Dawley rats underwent unilateral surgery to transect and repair the supraspinatus tendon to its insertion site with or without PEP. PEP promoted the migration and confluence of osteoblast cells and tenocytes, especially during direct cell-cell contact. Expression of potential genes for RCT in vitro and in vivo models were consistent with biomechanical tests and semiquantitative histologic scores, indicating accelerated strength and healing of the RC in response to PEP. Our observations suggest that circulating exosomes provide an effective option to improve the healing speed of RCT after surgical repair. The regeneration of enthesis following PEP treatment appears to be related to a mutually reinforcing relationship between direct cell-cell contact and PEP activity, suggesting a dual approach to the healing process.
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