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Adipose-derived stem cells improve tendon repair and prevent ectopic ossification in tendinopathy by inhibiting inflammation and inducing neovascularization in the early stage of tendon healing.
Regenerative Therapy ( IF 4.3 ) Pub Date : 2020-01-17 , DOI: 10.1016/j.reth.2019.12.003
Saeko Kokubu 1 , Ryoko Inaki 2 , Kazuto Hoshi 3 , Atsuhiko Hikita 2
Affiliation  

Introduction

Achilles tendinopathy is characterized by scar formation or ectopic ossification, both of which result in pain and worsened physical function in athletes and older people. Although cell therapy using adipose-derived stem cells (ASCs) has been shown to be effective for tendinopathy, the underlying mechanisms by which ASCs result in tendon healing in vivo have not yet been fully clarified.

Methods

ASCs were obtained from the fat pads of EGFP transgenic mice by collagenase digestion. C57BL/6 mice were used in a collagenase-induced injury model. ASCs were transplanted into injury sites at 1 week after injury. Tendons were harvested at 9 days, 2 weeks, and 4 weeks after transplantation, and analyzed by histological examination and μCT scanning.

Results

Histological analysis and μCT scanning revealed greater recovery of collagen fibers and suppression of ectopic ossification in the ASC-treated group than in the control group at 2 and 4 weeks after injury. Immunohistochemical analysis identified transplanted ASCs in the tendon core close to peritenon and connective tissue at 2 days and 1 week after transplantation, but not at 3 weeks. Furthermore, while the expression levels of IL-1β, GLUT1, and CA9 were significantly reduced in the ASC group compared to the control group at 9 days after injury, those of VEGF and the number of CD31 positive vessels were significantly increased.

Conclusion

The efficacy of ASCs for tendon repair and the prevention of ectopic ossification in Achilles tendinopathy were demonstrated. Our data suggest that ASCs can modulate inflammation and induce neovascularization in the early stage of tendon injury.



中文翻译:

脂肪干细胞通过在肌腱愈合的早期抑制炎症和诱导新血管形成来改善肌腱修复并预防肌腱病中的异位骨化。

介绍

跟腱病的特征是疤痕形成或异位骨化,这两者都会导致运动员和老年人的疼痛和身体机能恶化。尽管使用脂肪干细胞 (ASCs) 的细胞疗法已被证明对肌腱病有效,但 ASCs 导致体内肌腱愈合的潜在机制尚未完全阐明。

方法

通过胶原酶消化从 EGFP 转基因小鼠的脂肪垫中获得 ASC。C57BL/6 小鼠用于胶原酶诱导的损伤模型。损伤后 1 周将 ASC 移植到损伤部位。在移植后9天、2周和4周收获肌腱,并通过组织学检查和μCT扫描进行分析。

结果

组织学分析和 μCT 扫描显示,在损伤后 2 周和 4 周,ASC 治疗组的胶原纤维恢复和异位骨化抑制程度高于对照组。免疫组织化学分析在移植后 2 天和 1 周(但不是在 3 周)确定了靠近腹膜和结缔组织的腱核心中移植的 ASC。此外,虽然在损伤后 9 天,ASC 组的 IL-1β、GLUT1 和 CA9 的表达水平与对照组相比显着降低,但 VEGF 的表达水平和 CD31 阳性血管的数量显着增加。

结论

证明了 ASC 对跟腱修复和预防跟腱病异位骨化的功效。我们的数据表明,ASCs 可以在肌腱损伤的早期调节炎症并诱导新生血管形成。

更新日期:2020-01-17
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