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| 1 | An update–tissue engineered nerve grafts for the repair of peripheral nerve injuries显示文摘Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts(ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts(TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems(DDS), co-administration of platelet-rich plasma(PRP), and pretreatment with chondroitinase ABC(Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix(ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia(DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed. | Nitesh P.Patel Kristopher A.Lyon Jason H.Huang | 2018 | Neural Regeneration Research2018，13，5： | 12 |
| 2 | 复合脂肪来源干细胞的脱细胞异种神经联合富血小板血浆修复兔面神经损伤的实验研究显示文摘目的探讨复合脂肪来源干细胞(adipose-derived stem cells,ADSCs)的脱细胞异种神经联合富血小板血浆(platelet rich plasma,PRP)修复兔面神经损伤的早期效果。方法取15只3月龄雌性SD大鼠双侧坐骨神经进行脱细胞处理,作为异种神经移植体。取成年新西兰大耳白兔颈背部脂肪垫,采用Ⅰ型胶原酶单独消化法分离培养ADSCs;兔耳静脉采血后经两步离心法提取PRP;观察不同体积分数PRP对ADSCs增殖的影响,以及诱导其为类雪旺细胞可行性。取第3代ADSCs,CM-Dil活细胞染色剂标记后,荧光显微镜观察细胞标记及传代后荧光衰减情况。另取32只新西兰大耳白兔建立左侧面神经1 cm长缺损模型,随机分成4组(n=8),A、B、C、D组分别采用CM-Dil-ADSCs复合脱细胞异种神经+自体PRP、CM-Dil-ADSCs复合脱细胞异种神经、脱细胞异种神经、自体神经移植修复神经缺损。术后1、8周静态下测量各组动物左侧上唇与面正中线成角(θ角);4、8周神经电生理检测记录神经传导速度;8周荧光显微镜观察A、B组再生神经远近端CM-Dil-ADSCs数量,各组再生神经甲苯胺蓝染色计数有髓神经纤维、透射电镜观察再生神经纤维结构。结果 5%~20%PRP均能促进ADSCs增殖,经20%PRP诱导后细胞S-100免疫荧光染色呈阳性。ADSCs经CM-Dil标记后荧光显微镜下观察示细胞标记率达90%以上,被标记细胞传代后细胞增殖良好,传代后荧光稍衰减。术后各组动物均存活至实验完成。术后1周各组动物面部均发生不同程度功能障碍,A、B、C、D组左侧θ角分别为(53.4±2.5)、(54.0±2.6)、(53.7±2.4)、(53.0±2.1)°,均显著低于健侧(P<0.05);术后8周分别为(61.9±4.7)、(56.8±4.2)、(54.6±3.8)、(63.8±5.8)°,与健侧及术后1周比较差异均有统计学意义(P<0.05)。大体观察各组动物再生神经完整性及连续性均良好。术后4、8周神经电生理检测示,A、D组神经传导速度均显著快于B、C组,B组快于C组(P<0.05),A、D组间比较差异无统计学意义(P>0.05)。术后8周荧光显微镜观察示,A组移植神经远、近端横断面均可见大量CM-Dil-ADSCs通过,B组通过细胞相对较少。甲苯胺蓝染色示,A、D组有髓神经纤维密度均显著高于B、C组,B组高于C组(P<0.05);A、D组间差异无统计学意义(P>0.05)。透射电镜观察示,D组有髓神经纤维鞘直径大、壁厚,形态规则;A组髓鞘形态与D组相似;B、C组髓鞘形态不规则,直径小、壁薄。结论 ADSCs可以作为种子细胞在体内存活,并可在PRP诱导下分化为类雪旺细胞,与脱细胞异种神经复合后修复兔周围神经损伤可获得较好效果。 | 孙妍娜 张荣明 毛旭 张孟姝 | 2018 | 中国修复重建外科杂志2018，32，6： | 10 |
| 3 | Skeletal muscle-derived cells repair peripheral nerve defects in mice显示文摘Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cell group were not significantly different from the external oblique muscle-fabricated nerve conduit group.Collectively,these data suggest that muscle-derived cells effectively accelerated peripheral nerve regeneration.This study was approved by the Animal Ethics Committee of Plastic Surgery Hospital,Chinese Academy of Medical Sciences(approval No.040)on September 28,2016. | Zi-Xiang Chen Hai-Bin Lu Xiao-Lei Jin Wei-Feng Feng Xiao-Nan Yang Zuo-Liang Qi | 2020 | Neural Regeneration Research2020，15，1： | 7 |
| 4 | 脱细胞神经支架联合干细胞构建组织工程神经修复坐骨神经缺损的meta分析显示文摘背景:研究表明,脱细胞神经支架不仅具有天然神经的空间三维结构,而且具有低免疫原性,但对于长段神经缺损的修复效果仍不理想。为此,有学者将脱细胞神经支架复合种子细胞构建组织工程神经,以提高其治疗效果。目的:系统评价脱细胞神经支架联合间充质干细胞或许旺细胞移植修复大鼠坐骨神经缺损的疗效。方法:检索PubM ed、The Cochrane Library、EMbase、CNKI、WanF ang和VIP数据库,查阅关于脱细胞神经支架联合间充质干细胞或许旺细胞修复大鼠坐骨神经缺损的随机对照实验,检索时限均为建库至2016年7月。由3名研究员按纳入和排除标准独立筛选文献、提取数据和评价文献的方法学质量,采用Review Manger5.3软件进行meta分析。结果与结论:最终10篇文献纳入研究,共计252只大鼠。Meta分析结果显示:(1)脱细胞神经支架联合间充质干细胞或许旺细胞组的坐骨神经功能指数均优于单纯脱细胞神经支架组:2周[SMD=2.73,95%CI(1.92,3.54),P<0.000 01],4周[SMD=4.57,95%CI(3.43,5.70),P<0.000 01],6周[SMD=1.62,95%CI(0.18,3.06),P=0.03],8周[SMD=4.90,95%CI(2.96,6.84),P<0.000 01];(2)术后12周脱细胞神经支架联合间充质干细胞或许旺细胞组神经传导速度、潜伏期、振幅优于脱细胞神经支架组:神经传导速度[SMD=1.39,95%CI(0.99,1.78),P<0.000 01],潜伏期[MD=-0.98,95%CI(-1.19,-0.76),P<0.000 01],振幅[SMD=1.23,95%CI(0.62,1.85),P<0.000 1];(3)脱细胞神经支架联合间充质干细胞或许旺细胞组髓鞘厚度均优于单纯脱细胞神经支架组:术后8周髓鞘厚度[MD=0.14,95%CI(0.07,0.21),P<0.000 1],术后12周髓鞘厚度[SMD=1.85,95%CI(1.63,2.08),P<0.000 01],术后12周有髓神经纤维数[SMD=3.59,95%CI(2.63,4.55),P<0.000 01];(4)术后8周脱细胞神经支架联合间充质干细胞或许旺细胞组腓肠肌湿重优于单纯脱细胞神经支架组[SMD=4.22,95%CI(2.40,6.03),P<0.000 01];(5)当前证据表明,脱细胞神经支架联合间充质干细胞或许旺细胞治疗大鼠坐骨神经缺损较单纯脱细胞神经支架更有助于神经再生和功能恢复。受纳入文献质量的限制,以上结论需更高质量、更大样本的随机对照实验加以验证。 | 向飞帆 阳运康 谭小琦 魏代清 杨琨 孙远林 周举 | 2017 | 中国组织工程研究2017，21，22： | 3 |
| 5 | 神经生长因子和第10号染色体同源丢失性磷酸酶-张力蛋白基因双基因修饰骨髓间充质干细胞促进周围神经再生显示文摘目的探讨神经生长因子(nerve growth factor,NGF)和第10号染色体同源丢失性磷酸酶-张力蛋白基因(phosphatase and tensin homolog deleted on chromosome 10,PTEN)双基因修饰的骨髓间充质干细胞促进周围神经再生。方法通过构建NGF稳定转染的骨髓间充质干细胞株,PTEN基因的siRNA瞬时转染NGF-BMSC稳转株,构建双基因修饰的BMSC。采用切断坐骨神经法构建周围神经损伤模型,BMSC移植治疗,随机分为空白对照组,普通细胞组和双基因修饰组。采用SFI测定实验和肌湿重恢复率测量实验检测损伤神经元的功能恢复情况,利用Nestin-1免疫组化染色,HE和LFB染色以及透射电镜下观察再生神经超微结构,检测损伤后的神经元的分化和再生能力。结果双基因修饰组BMSC治疗后神经功能恢复能力明显强于普通细胞治疗组(P<0.05);双基因修饰的骨髓间充质干细胞在神经损伤局部能更好地存活,分布更广;双基因修饰组BMSC治疗后,神经分化能力更强,更能促进神经轴突和髓鞘再生。结论NGF基因的过表达和PTEN基因的沉默的双重修饰的BMSC,能够更好地促进周围神经损伤后神经元的分化和再生能力,达到更好的治疗效果。 | 陈毅 林平 吴咏军 涂迎春 李焘 赵有顺 黄志丹 | 2020 | 中华手外科杂志2020，36，4： | 3 |
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