Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons.
Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons.
复制标题
基本 FGF 或 VEGF 基因治疗可纠正肌腱内在愈合能力的不足
DOI：
10.1038/srep20643
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发表时间：
2016-02-11
影响因子：
4.6
通讯作者：
Liu PY
中科院分区：
文献类型：
--
作者：
Tang JB;Wu YF;Cao Y;Chen CH;Zhou YL;Avanessian B;Shimada M;Wang XT;Liu PY
肢体运动时肌腱损伤是常见的。受损的肌腱愈合不良，并且由于先天愈合能力不足，经常发生不可预测的破裂或运动受损。通过腺相关病毒2型（AAV 2）载体介导的碱性成纤维细胞生长因子（bFGF）或血管内皮生长因子（VEGF）基因治疗，使肌腱内在产生超常量的bFGF或VEGF，有效纠正肌腱愈合能力不足。这种治疗方法（1）导致治疗肌腱中低生长因子活性的显著改善，从第4周到第6周bFGF或VEGF显著增加（p < 0.05或p < 0.01），（2）显著促进I型胶原蛋白和其他细胞外分子的产生（3）与对照组相比，AAV 2-bFGF治疗后第2周肌腱强度显著增加68-91%，AAV 2-VEGF治疗后第3周肌腱强度显著增加82- 210（p < 0.05或p < 0.01）。此外，愈合完成后转基因表达消失。这些结果表明，基因转移提供了一个乐观的解决方案的内在愈合能力的肌腱的不一致性，并提供了一个有效的治疗肌腱不愈合的患者的可能性。
Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation and (3) significantly increased tendon strength by 68–91% from week 2 after AAV2-bFGF treatment and by 82–210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion.