Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA.
Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA.
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DOI：
10.22203/ecm.v023a07
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发表时间：
2012-02-16
影响因子：
3.1
通讯作者：
Evans CH
中科院分区：
文献类型：
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作者：
Majewski M;Porter RM;Betz OB;Betz VM;Clahsen H;Flückiger R;Evans CH
肌腱断裂是一种常见的损伤。内源性修复不当往往会使患者出现症状，肌腱容易再次断裂。在动物模型中，某些生长因子的应用可以促进肌腱的愈合，但它们的释放仍然是一个挑战。在这里，我们评估了通过植入转基因肌肉移植物将转化生长因子-β1转移到肌腱缺损处的情况。用编码转化生长因子β1的重组腺病毒转导大鼠肌肉活检组织，并将其移植到受体动物手术切除的跟腱上。通过生物力学测试以及组织化学和免疫组织化学分析，将组织再生与对照组进行比较。当将转基因移植物植入肌腱缺损处时，愈合速度大大加快，所产生的修复组织最早在术后2周就获得了接近正常的组织学外观。这与III型胶原沉积减少有关，有利于I型胶原的大纤维束。肌腱成分的这些差异与机械强度的加速恢复相吻合。基因治疗的动物在第一周和第二周肌腱厚度增加，但到第八周变得明显低于对照组，这表明加速了肌腱的重塑。因此，通过腺病毒修饰的肌肉移植物局部传递转化生长因子-β-1改善了这种大鼠模型的肌腱愈合，并为临床应用提供了希望。
Tendon rupture is a common injury. Inadequate endogenous repair often leaves patients symptomatic, with tendons susceptible to re-rupture. Administration of certain growth factors improves tendon healing in animal models, but their delivery remains a challenge. Here we evaluated the delivery of TGF-β1 to tendon defects by the implantation of genetically modified muscle grafts. Rat muscle biopsies were transduced with recombinant adenovirus encoding TGF-β1 and grafted onto surgically transected Achilles tendons in recipient animals. Tissue regenerates were compared to those of controls by biomechanical testing as well as histochemical and immunohistochemical analyses. Healing was greatly accelerated when genetically modified grafts were implanted into tendon defects, with the resulting repair tissue gaining nearly normal histological appearance as early as 2 weeks postoperatively. This was associated with decreased deposition of type III collagen in favour of large fibre bundles indicative of type I collagen. These differences in tendon composition coincided with accelerated restoration of mechanical strength. Tendon thickness increased in gene-treated animals at weeks 1 and 2, but by week 8 became significantly lower than that of controls suggesting accelerated remodelling. Thus localised TGF-β1 delivery via adenovirus-modified muscle grafts improved tendon healing in this rat model and holds promise for clinical application.