背景:跟腱病以瘢痕形成或异位骨化为特征,两者都会导致运动员和老年人的疼痛和身体功能恶化。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,ASCs在体内导致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获得ASC。在胶原酶诱导的损伤模型中使用C57BL/6小鼠。在损伤后1周将ASC移植到损伤部位。在9天收获肌腱,2周,移植后4周,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,损伤后2周和4周,ASC治疗组比对照组有更大的胶原纤维恢复和异位骨化抑制。免疫组织化学分析确定移植后2天和1周时,肌腱核心中靠近周围和结缔组织的移植ASC,但不是在3周。此外,而IL-1β的表达水平,损伤后第9天,ASC组的GLUT1和CA9与对照组相比显着降低,VEGF和CD31阳性血管的数量明显增加。
结论:证实了ASCs在跟腱病肌腱修复和预防异位骨化方面的有效性。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。
BACKGROUND: 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.
CONCLUSIONS: 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.