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
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
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DOI：
10.1016/j.reth.2019.12.003
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发表时间：
2020-06-01
影响因子：
4.3
通讯作者：
Hikita, Atsuhiko
中科院分区：
文献类型：
--
作者：
Kokubu, Saeko;Inaki, Ryoko;Hikita, Atsuhiko
简介：跟腱病的特征是疤痕形成或异位骨化，这两种情况都会导致运动员和老年人的疼痛和身体功能恶化。虽然使用脂肪来源的干细胞（ASCs）的细胞疗法已被证明是有效的肌腱病，ASCs的结果在体内肌腱愈合的潜在机制尚未完全cleared.Methods：ASCs获得的EGFP转基因小鼠的脂肪垫通过胶原酶消化。C57 BL/6小鼠用于胶原酶诱导的损伤模型。于伤后1周将ASC移植于损伤部位。肌腱收获9天，2周，4周后移植，并通过组织学检查和mCT scanning.Results：组织学分析和mCT扫描显示更大的恢复胶原纤维和抑制异位骨化的ASC治疗组比对照组在2和4周后损伤。免疫组化分析表明，移植后2天和1周，在肌腱核心靠近腱周和结缔组织处有移植的ASC，但3周时没有。此外，虽然IL-1 β，GLUT 1，和CA 9的表达水平显着降低ASC组相比，对照组在9天后的损伤，VEGF和CD 31阳性vessels的数量显着increased.Conclusion：ASCs肌腱修复和异位骨化的预防跟腱病的疗效被证明。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。(c)2020年，日本再生医学学会。由Elsevier B. V.制作和托管。这是CC BY-NC-ND许可证下的开放获取文章（http：creativecommons.org/licenses/by-nc-nd/ 4.0/）。
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 mCT scanning.Results: Histological analysis and mCT 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-1 beta, 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. (c) 2020, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).