Tang Jin Bo, Wu Ya Fang, Cao Yi, Chen Chuan Hao, Zhou You Lang, Avanessian Bella, Shimada Masaru, Wang Xiao Tian, Liu Paul Y
The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Department of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School, Brown University, Providence, RI, USA.
Sci Rep. 2016 Feb 11;6:20643. doi: 10.1038/srep20643.
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.
肢体运动过程中的肌腱损伤很常见。受损肌腱愈合不佳，由于先天愈合能力不足，常常会发生不可预测的断裂或运动功能受损。通过腺相关病毒2型（AAV2）载体进行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，使肌腱内源性产生超常数量的bFGF或VEGF，我们有效地纠正了肌腱愈合能力的不足。这种治疗方法（1）导致低生长因子活性得到显著改善，在治疗后的肌腱中，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（p < 0.01），并加速细胞增殖；（3）与对照组相比，AAV2 - bFGF治疗后第2周肌腱强度显著增加68 - 91%，AAV2 - 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。这些发现表明，基因转移为肌腱固有愈合能力不足提供了一个乐观的解决方案，并为肌腱不连患者提供了一种有效的治疗可能性。
