Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

中文翻译：

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低氧诱导的间充质干细胞表现出更强的腱分化能力并促进Pro骨腱修复。

肌腱损伤是常见但棘手的医学问题。据报道，使用间充质干细胞（MSC）治疗肌腱修复的临床结果不理想，因此需要一种更好的策略来诱导MSCs向肌腱分化。本研究旨在探讨缺氧对不同MSCs的腱向分化的影响及其在体外低氧条件下的腱向分化能力，并研究缺氧在腱鞘生成中的体内诱导性。分离并表征了脂肪组织来源的MSC（AMSC）和骨髓来源的MSC（BMSC）。低氧诱导的因子1α（Hif- 1α）检查以确认是否存在缺氧状况。使用qRT-PCR，western印迹和免疫荧光染色来评估在缺氧条件下AMSC和BMSC中与肌腱相关的标志Col-1a1，Col-3a1，Dcn和Tnmd的表达，与Tgf- β1诱导相比。在体内，建立a腱损伤模型。培养并植入常氧和低氧的BMSC。进行了组织学，生物力学和透射电镜分析，以评估缺氧性BMSC对肌腱损伤的改善愈合效果。我们的体外结果表明，低氧显着增加了Hif- 1α的表达与低氧组相比，低氧不仅促进了AMSCs和BMSCs的肌腱标志物显着增加，而且与Tgf- β1相比，还显示出更高的诱导能力。此外，低氧BMSCs与低氧AMSCs相比具有更高的肌腱分化潜力。我们的体内结果表明，低氧BMSCs具有比常氧BMSCs更好的组织学和生物力学特性，这在组织学评分，pa腱生物力学参数以及胶原纤维直径的范围和平均值中得到了证明。这些发现表明，低氧可能是诱导BMSCs肌腱分化的肌腱修复的实用且可靠的策略，并且可以增强MSCs治疗肌腱损伤的有效性。