Luo Lihua, Gan Li, Liu Yongming, Tian Weiqun, Tong Zan, Wang Xiong, Huselstein Celine, Chen Yun
Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053, China.
Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Biochem Biophys Res Commun. 2015 Feb 20;457(4):507-13. doi: 10.1016/j.bbrc.2014.12.121. Epub 2015 Jan 9.
Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide conduits in the field of nerve tissue engineering.
周围神经缺损的再生和功能重建仍然是一项重大的临床挑战。带有种子细胞或神经营养因子(NTFs)的神经导管已被广泛用于改善受损周围神经的修复和再生。吡咯喹啉醌(PQQ)是一种抗氧化剂,可刺激神经生长因子(NGFs)的合成,并加速雪旺细胞(SCs)的增殖和生长。在本研究中,分别构建了三种神经导管:一种由纤维素/大豆分离蛋白中空管(CSC)制成,另一种由CSC与SCs组合而成(CSSC),第三种由CSSC与PQQ组合而成(CSSPC)。然后将它们应用于桥接和修复大鼠坐骨神经缺损,以自体移植作为对照。通过综合分析、坐骨神经功能指数(SFI)和组织学分析(HE和TEM)对不同神经导管对神经再生的影响进行了比较评估。术后12周观察到新形成的再生神经纤维穿过透明的神经导管。SFI结果表明,CSSPC组的运动功能重建优于CSSC组和CSC组。收获的再生神经横截面和纵截面的HE图像表明,再生神经纤维已经形成,并伴有导管内的新血管和基质材料。TEM图像还显示形成了许多新鲜的有髓和无髓神经纤维。CSC组和CSSC组出现部分空泡化、肿胀和异常轴突,而CSSPC组轴突的空泡化和肿胀最不严重。这些结果表明,由于中空CSC管、SCs和PQQ的综合作用,CSSPC组修复和重建神经结构及功能的能力最强。因此,CSSPC在神经组织工程领域作为神经导管应用可能具有潜力。