神经干细胞移植联合腹腔注射促红细胞生成素对横断性脊髓损伤大鼠神经轴突的修复作用

doi:10.13481/j.1671-587x.20150119

Abstract

Abstract:

Objective To investigate the repair effect of neural stem cells(NSCs) and erythropoietin (EPO) on the axonal regeneration of the rats with transected spinal cord injury in spinal cord injury area, and to provide theoretical basis for the clinical treatment of spinal cord injury. Methods Forty Wistar rats with T10 spinal cord transaction were randomly divided into control group, NSCs group, EPO group and NSCs+EPO group(n=10).BDA anterograde corticospinal cord neuronal tracing and fluoro-gold(FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers.The BBB locomotion score was used to evaluate the restoration after operation in the rats with spinal cord transaction. Results The BDA immunofluorescence staining and FG immunofluorescence staining results showed that a large amount of regenerated axons were observed in NSCs+EPO group, which were labeled by BDA-cy3 red fluorescence, and some regenerated axons got through the injuried area.While in NSCs group, only a small amount of regenerated axons were observed after spinal cord injury, and no regenerated axons got through the injuried area.In EPO group, only sporadically regenerated nerve fibers were observed occasionally, while in control group, no axonal regeneration was observed.In NSCs+EPO group, a small amount of cones and axons, which were labeled by FG fluorescence, emitted golden yellow fluorescence, and no cells labeled by FG was observed in other groups.The BBB scores in NSCs+EPO group 7 d after operation and at different time later were higher than those in other groups(P<0.05). Conclusion Transplantated NSCs and intraperitoneal injection of EPO could promote axon regeneration in spinal cord injury zone and hind limb motor function recovery of the rats with spinal cord injury.

Key words: neural stem cells, erythropoietin, stem cell transplantation, transected spinal cord injury, axonal regeneration

CLC Number:

R681.54

WANG Xiliang, ZHAO Yan, ZUO Yuan, XIAO Yulong, HUO Hongjun, JIANG Jianming, YAN Huibo. Repaireffect of neural stem cells transplantation combined with intraperitoneal injection erythropoietin for axons in adult rats with transected spinal cord injury[J].Journal of Jilin University Medicine Edition, 2015, 41(01): 99-104.

References

[1] 武俏丽,李庆国,刘暌.干细胞移植治疗脊髓损伤研究进展[J].中国组织工程研究与临床康复,2008,12(12):2343-2346.

[2] Bukovsky A,Caudle MR,Svetlikova M.Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro[J].Cell Cycle,2008,7(22):3577-3583.

[3] Bethea CL,Reddy AP,Pedersen D,et al.Expression profile of differentiating serotonin neurons derived from rhesus embryonic stem cells and comparison to adult serotonin neurons[J].Gene Expr Patterns,2009,9(2):94-108.

[4] 胡萌,吕刚.神经干细胞移植治疗脊髓损伤的研究与现状[J].中国组织工程研究与临床康复,2009,13(19):3751-3754.

[5] Cai PQ,Sun GY,Cai PS,et al.Survival of transplanted neurotrophin-3 expressing human neural stem cells and motor function in a rat model of spinal cord injury[J].Neural Regen Res,2009,4(7):485-491.

[6] Chigr F,Rachidi F,Segura S,et al.Neurogenesis inhibition in the dorsal vagal complex by chronic immobilization stress in the adult rat[J].Neuroscience,2009,158(2):524-536.

[7] Andres RH,Horie N,Slikker W,et al.Human neural stem cells en-hance structural plasticity and axonal transport in the ischaemic brain[J].Brain,2011,134(6):1777-1789.

[8] Sanchis-Gomar F,Perez-Quilis C,Lippi G,et al.Erythropoietin receptor (EPOR) agonism is used to treat a wide range of disease[J].Mol Med,2013,19(1):62-64.

[9] 徐富翠,邹礼乐,梅欣明,等.神经干细胞培养及其影响因素[J].中国组织工程研究,2013,17(10):1835-1840.

[10] 张殿君,刘一,付长峰,等.新生大鼠脊髓源性神经干细胞的分离培养及分化鉴定[J].吉林大学学报:医学版,2009,35(2):230-233.

[11] Ozsoy O,Ozsoy U,Stein G,et al.Functional deficits and morphological changes in the neurogenic bladder match the severity of spinal cord compression[J].Restor Neurol Neurosci,2012,30(5):363-381.

[12] 孟步亮,巴迎春,宋士娜,等.脊髓全横断大鼠模型的构建[J].中国组织工程研究与临床康复,2011,15(7):1215-1218.

[13] Salazar DL,Uchida N,Hamers FP,et al.Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model[J].PLoS One,2010,5(8):1-15.

[14] 王星星,查伟光,易林华,等.生物素葡聚糖胺皮质脊髓束顺行示踪技术在大鼠脊髓损伤模型中的应用[J].中华神经外科杂志,2004,20(1):51-54.

[15] 巴迎春,唐建中,范艳,等.生物素多聚葡聚糖胺追踪显示皮质脊髓束的走行和分布[J].中国组织工程研究,2012,16(24):4447-4452.

[16] Parr AM,Kulbatski I,Tator CH.Transplantation of adult rat spinal cord stem/progenitor cells for spinal cord injury[J].Neurotrauma,2007,24(5):835-845.

[17] Watt FM,Hogan BLM.Out of eden:stem cells andtheir niches [J].Science,2000,287(5457):1427-1430.

[18] Hermanson O,Jepsen K,Rosenfeld MG.N-CoR controls differentiation of neural stem cells into astrocytes[J].Nature,2002,419 (6910) :934-939.

[19] Kang SY,Kang JH,Choi JC,et al.Expression of erythropoietin in the spinal cord of lewis rats with experimental autoimmune encephalomyelitis[J].J Clin Neurol,2009,5(1):39-45.

[20] 袁丽丽,杜红梅,管英俊,等.促红细胞生成素体外培养鼠胚脑皮质神经干细胞的分化[J].中国组织工程研究与临床康复,2011,15(49):9174-9177.

[21] Nakamura M,Toyama Y,Okano H.Transplantation of neural stem cells for spinal cord injury [J].Rinsho Shinkeigaku,2005,45(11):874-876.

Repaireffect of neural stem cells transplantation combined with intraperitoneal injection erythropoietin for axons in adult rats with transected spinal cord injury

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 14

Metrics

Comments

Recommended 0

[1]	LIU Linna, CHEN Jieyu, LYU Fangyi, HUA Kouzhen, CAI Damin, YIN Guoli, WANG Junjuan. Effect of fingolimod on proliferation and migration of neural stem cells and astrocytes and its protective mechanism against spinal cord injury in mice [J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1218-1222.
[2]	PENG Yinyin, CHEN Liping, LIU Lin, CHEN Jianbin, CHEN Yajuan, HAN Xiaoli, XIAO Qing. Rituximab-induced interstitial lung disease:A case report and literature review [J]. Journal of Jilin University Medicine Edition, 2017, 43(06): 1260-1264.
[3]	LIU Wenbin, XU Yan, LI Zhimeng, ZHOU Jia, HUANG Xiaowei. Effects of Shen Hong Bu Xue Granule on expressions of EPO mRNA in kidney tissue and GM-CSF mRNA in bone marrow tissue in mice with blood deficiency [J]. Journal of Jilin University Medicine Edition, 2017, 43(03): 538-542.
[4]	HAN Xueli, LIU Dong, ZHANG Xiujuan, ZHOU Ying. Evaluation effect of autologous bone marrow stem cell transplantation combined with percutaneous endovascular angioplasty in treatment of diabetic foot [J]. Journal of Jilin University Medicine Edition, 2016, 42(01): 125-129.
[5]	ZHU Yang, LI Daowei, FANG Tengjiaozi, SHI Ce, WANG Dandan, SUN Hongchen. Promotive effect of PLGA nanofiber scaffold adsorped Epo gene mediated by adenovirus on bone defect repair [J]. Journal of Jilin University Medicine Edition, 2015, 41(04): 711-715.
[6]	ZHAO Yan, XIAO Yulong, ZUO Yuan, WANG Xiliang, HUO Hongjun, JIANG Jianming, YAN Huibo. Repair effect of neural stem cells transplantation combined with erythropoietin on spinal cord injury in rats [J]. Journal of Jilin University Medicine Edition, 2015, 41(02): 333-337.
[7]	QIU Jiong, ZHAO Yu-wei, LI Fa-qi, ZHOU Ping, LI Wan-yu. Protective effect of erythropoietin on myocardium of \|rats with ischemia-reperfusion injury [J]. J4, 2012, 38(5): 912-917.
[8]	ZHANG Guo-xing,SUN Yu,SUN Ni\|LI Xiu-jiang,DU Yu-jun. Protective effect of erythropoietin on lipopolysaccharide -induced liver injury in rats [J]. J4, 2012, 38(3): 456-460.
[9]	CUI Li, ZHANG Ju, LIN Wei-Gong, MA Di-Hui, JI E-Li, FU Hai-Long, SUN Jiang, CHANG Meng, LV Xiao-Gong. Injury of neural stem cells cultured in vitro induced by glutamate of embryonic rats [J]. J4, 2009, 35(3): 451-455.
[10]	ZHANG Dian-jun,LIU Yi,FU Chang-feng,SU Xiao-yun,WANG Fang,LI Xiang-jun. Sepration，cultivation and differentiation of neural stem cells from newborn rat spinal cords [J]. J4, 2009, 35(2): 230-232.
[11]	MA Xue-ling，LIU Kang-ding，JIANG Xin-mei，WEN Jia-mei，LI Gui-yu，LI Nan. Effects of orientation transplantation of human bone marrow mesenchymal　stem cells on behavioral tests of focal cerebral ischemia in rats [J]. J4, 2007, 33(3): 427-431.
[12]	WANG Ji， LUO Ping， ZHANG Dong-mei. Effects of r-HuEPO on RBC immunity in CRF patients [J]. J4, 2006, 32(6): 1071-1073.
[13]	LIU Ya-juan,LI Xiu-dong,CHEN Qiang, LING Ling,LIU Li-zhu, FAN Hong-xue. Induction of mesenchymal stem cells into islet-like cellsin vitro and its repair on injured pancreas tissues [J]. J4, 2005, 31(6): 836-838.
[14]	MENG Xiao-ting, CHEN Dong,LIU Jia-mei, LU　Lai-jin. Enhanced viability and neural differentiation of neural stemcells co-cultured with amniotic epithelial cells [J]. J4, 2004, 30(2): 184-187.