Hoben Gwendolyn, Yan Ying, Iyer Nisha, Newton Piyaraj, Hunter Dan A, Moore Amy M, Sakiyama-Elbert Shelly E, Wood Matthew D, Mackinnon Susan E
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Avenue, St. Louis, MO 63110 USA.
Department of Biomedical Engineering, Washington University, Campus Box 1097, One Brookings Drive, St. Louis, MO 63130 USA.
Hand (N Y). 2015 Sep;10(3):396-402. doi: 10.1007/s11552-014-9720-0.
Individual contributions of exogenous Schwann cells (SCs) and vascular endothelial growth factor (VEGF) were evaluated in acellular nerve allografts (ANAs). ANA processing removes SCs and vasculature, likely contributing to reduced regeneration compared to autografts. Exogenous SCs may improve the regenerative microenvironment, and VEGF has been shown to stimulate angiogenesis. Replacing these components in ANAs may improve regeneration.
A rat sciatic nerve transection model was used to study 20-mm grafts. Four graft types were studied: (1) isograft, (2) ANA, (3) ANA-SCs, and (4) ANA-VEGF. After 10 weeks in vivo, the midgraft and distal nerve to the grafts were analyzed for axonal regeneration using histomorphometry to assess total myelinated axon counts, density, width, and percent neural tissue.
The most axons in the distal nerve were regenerated in the isograft followed by the ANA- SC group, with 9171 ± 1822 and 7103 ± 1576 regenerated axons respectively. Both the ANA and ANA-VEGF groups had significantly fewer regenerated axons compared to the isograft (p < 0.05) with 5225 ± 2994 and 5709 ± 2657 regenerated axons, respectively. The ANA and ANA-VEGF groups also had significantly reduced fiber density and percent nerve compared to the isograft; the isograft and ANA-SC groups were not significantly different (p < 0.05).
These results show that SCs improve axonal regeneration in a 20 mm ANA to a greater extent than VEGF. VEGF treatment showed a trend toward increased axonal regeneration but was not significantly different compared to the untreated ANA. The role of VEGF may be clearer in longer grafts where ischemia is a greater factor.
评估了外源性雪旺细胞(SCs)和血管内皮生长因子(VEGF)在脱细胞神经同种异体移植物(ANAs)中的个体作用。ANA处理去除了SCs和脉管系统,这可能是与自体移植物相比再生减少的原因。外源性SCs可能改善再生微环境,并且VEGF已被证明可刺激血管生成。在ANAs中替换这些成分可能会改善再生。
使用大鼠坐骨神经横断模型研究20毫米移植物。研究了四种移植物类型:(1)同基因移植物,(2)ANA,(3)ANA-SCs,和(4)ANA-VEGF。在体内10周后,使用组织形态计量学分析移植物中段和移植物远端神经的轴突再生,以评估总髓鞘轴突计数、密度、宽度和神经组织百分比。
同基因移植物中远端神经再生的轴突最多,其次是ANA-SC组,分别有9171±1822和7103±1576条再生轴突。与同基因移植物相比,ANA和ANA-VEGF组的再生轴突明显更少(p<0.05),分别有5225±2994和5709±2657条再生轴突。与同基因移植物相比,ANA和ANA-VEGF组的纤维密度和神经百分比也显著降低;同基因移植物和ANA-SC组无显著差异(p<0.05)。
这些结果表明,SCs比VEGF在20毫米的ANA中能更大程度地改善轴突再生。VEGF治疗显示出轴突再生增加的趋势,但与未治疗的ANA相比无显著差异。在缺血是更大因素的更长移植物中,VEGF的作用可能更明显。