Exosomes from tendon stem cells promote injury tendon healing through balancing synthesis and degradation of the tendon extracellular matrix
Exosomes from tendon stem cells promote injury tendon healing through balancing synthesis and degradation of the tendon extracellular matrix
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来自肌腱干细胞的外泌体通过平衡肌腱细胞外基质的合成和降解来促进损伤肌腱的愈合
DOI：
10.1111/jcmm.14430
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发表时间：
2019-08-01
影响因子：
5.3
通讯作者：
Tang, Kanglai
中科院分区：
文献类型：
--
作者：
Wang, Yunjiao;He, Gang;Tang, Kanglai
肌腱损伤是临床常见的肌肉骨骼系统疾病，但肌腱的再生能力有限。肌腱干细胞在组织工程中显示出良好的应用前景，已被用于肌腱损伤的治疗。外泌体作为遗传信息的载体参与了许多疾病和生理过程，但其对肌腱损伤修复的影响尚不清楚。本研究的目的是明确来自TSC的外泌体对肌腱损伤愈合的影响。通过连续离心过程从TSC的条件培养基收获外来体。采用Ⅰ型胶原酶注射法建立大鼠跟腱病模型。随后是跟腱内注射TSC或外来体。伤后5周行组织学观察和生物力学测试，评价肌腱愈合和基质降解情况。在体外，用白细胞介素1 β处理的TSCs加入包括或不包括外泌体的条件培养基，或者加入外泌体或不加入外泌体。采用免疫组化和蛋白质印迹法检测肌腱基质相关标志物和肌腱形成相关标志物。我们发现，TSCs注射和外泌体注射显著降低基质金属蛋白酶（MMP）-3的表达，增加金属蛋白酶组织抑制剂-3（TIMP-3）和Col-1a 1的表达，并增加极限应力和最大载荷的生物力学性能。在体外，条件培养基与exosomes和exosomes也显着降低MMP-3，并增加表达tenomodulin，Col-1a 1和TIMP-3。来源于TSCs的Exosomes能够平衡肌腱细胞外基质，促进TSCs的腱生成，是肌腱损伤修复的理想治疗策略。
Tendon injuries are common musculoskeletal system disorders in clinical, but the regeneration ability of tendon is limited. Tendon stem cells (TSCs) have shown promising effect on tissue engineering and been used for the treatment of tendon injury. Exosomes that serve as genetic information carriers have been implicated in many diseases and physiological processes, but effect of exosomes from TSCs on tendon injury repair is unclear. The aim of this study is to make clear that the effect of exosomes from TSCs on tendon injury healing. Exosomes were harvested from conditioned culture media of TSCs by a sequential centrifugation process. Rat Achilles tendon tendinopathy model was established by collagenase-I injection. This was followed by intra-Achilles-tendon injection with TSCs or exosomes. Tendon healing and matrix degradation were evaluated by histology analysis and biomechanical test at the post-injury 5 weeks. In vitro, TSCs treated with interleukin 1 beta were added by conditioned medium including exosomes or not, or by exosomes or not. Tendon matrix related markers and tenogenesis related markers were measured by immunostaining and western blot. We found that TSCs injection and exosomes injection significantly decreased matrix metalloproteinases (MMP)-3 expression, increased expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and Col-1a1, and increased biomechanical properties of the ultimate stress and maximum loading. In vitro, conditioned medium with exosomes and exosomes also significantly decreased MMP-3, and increased expression of tenomodulin, Col-1a1 and TIMP-3. Exosomes from TSCs could be an ideal therapeutic strategy in tendon injury healing for its balancing tendon extracellular matrix and promoting the tenogenesis of TSCs.