嗅鞘细胞对螺旋神经节细胞离体培养的影响及其机制的研究
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摘要
第一部分嗅鞘细胞的体外培养、纯化及鉴定
目的：纯化培养和鉴定成年大鼠嗅球嗅鞘细胞(olfactory ensheathing cells OECs),为后续实验做好准备。方法：取成年大鼠嗅球神经层,经酶消化的方法获得含有OECs的混合细胞悬液,采用多次长时差速贴壁的方法纯化OECs,用含有10%FBS的DF12培养基培养,2d后培养基中加入bFGF (20ng/ml)和forskolin(2uM)促进OECs的增殖,每隔3d半量更换培养基。倒置相差显微镜下观察OECs的生长状态,采用P75NTR和GFAP细胞免疫组化的方法鉴定OECs,荧光显微镜下观察OECs的形态并统计其纯度。结果：采用多次长时差速贴壁的方法能够去除绝大部分的污染细胞,包括成纤维细胞和星形胶质细胞,接种的OECs约24小时后贴壁,倒置相差显微镜下观察见大部分细胞胞体呈梭形、部分细胞胞体为多角形,伸出突起；细胞在接种培养的前2d生长缓慢,2d后培养基中加入bFGF (20ng/ml)和forskolin(2uM)可见细胞增殖加快,细胞突起细长,培养7d后见OECs覆盖皿底的90%,形成—细胞单层。P75NTR和GFAP染色见约92%的细胞为P75NTR(+),分布在突起、胞体,其中胞核被深染；约12%的细胞为GFAP (+)。结论：采用多次长时差速贴壁的方法能够获得实验所需纯度的OECs,培养基(DF12+10%FBS)中加入bFGF(20ng/ml)和forskolin(2uM)能够显著促进OECs的增殖。
第二部分嗅鞘细胞对耳蜗螺旋神经节细胞离体培养的影响
目的：探索在离体实验中OECs有无促进耳蜗听觉传入神经元—螺旋神经节细胞(spiral ganglion cells SGCs)存活的作用。方法：取成年大鼠嗅球和新生大鼠蜗轴组织块进行OECs与SGCs的培养,采用多次长时差速贴壁的方法纯化培养OECs。实验分OECs与SGCs共培养组、SGCs在OECs条件培养液中(OEC-CM)培养组和SGCs单独培养组。倒置相差显微镜下观察OECs和SGCs生长状态,P75NTR免疫组化法鉴定OECs,神经元特异性标志物βⅢ-tubulin标记SGCs。结果：OECs贴壁培养7天后形成—细胞单层,在OECs与SGCs共培养体系中,SGCs在OECs形成的细胞单层的表面生长,并伸出长突起,呈现典型的双极神经元形态；在培养的前6d,随着培养时间的延长,SGCs较接种前减少,但共培养组中SGCs存活数量明显高于SGCs单独培养组(P<0.01)；与SGCs在OEC-CM中培养比较,共培养组更能促进SGCs存活,并且单独培养组的SGCs数量在培养的第6d出现大幅度减少；在培养的第9d,单独培养组中几乎没有SGCs生长；而在共培养组,SGCs的数量未见明显变化(P>0.05)；统计发现单独培养组中存活的SGCs由第3d的14.6±1.1SGCs/视野(×200)减少到第14d的3.3±0.3SGCs/视野；OEC-CM组中的SGCs由35.3±2.1SGCs/视野下降到12.9±0.3SGCs/视野；共培养组中存活的SGCs较其它组明显增多,由第3d的66.9±1.2SGCs/视野(×200)减少到第14d的38.9×1.0 SGCs/视野。结论：OECs与SGCs共培养能够促进新生大鼠SGCs存活。
第三部分嗅鞘细胞促进螺旋神经节细胞存活的分子机制
目的：初步研究OECs促进SGCs体外存活的分子机制。方法：建立OECs与SGCs共培养体系,实验分三组：共培养+脑源性神经营养因子(BDNF,500 pg/ml)组；共培养+BDNF抗体(IgY型,50 ug/ml)组；对照组为OECs与SGCs共培养。共培养3d后固定,βⅢ-tubulin免疫组化染色鉴定SGCs,每个培养皿随机取4个视野,荧光显微镜下统计βⅢ-tubulin标记的SGCs,统计各培养组中的SGCs。结果：共培养+BDNF组中有大量SGCs在OECs形成的单层细胞毯表面生长,但与对照组比较,SCG的数目无统计学差异；加入BDNF抗体(IgY)的共培养组中的SGCs数量明显减少(P<0.01)。结论：OECs与SGCs共培养中加入BDNF对SGCs存活无明显影响,而加入BDNF抗体(IgY)后存活的SGCs减少。OECs分泌BDNF可能是其促进SGCs体外培养的存活,发挥对SGCs的营养保护作用的分子机制之一。
Part 1 Culture, purification and identification of olfactory ensheathing cells
Objective:To culture and purify olfactory ensheathing cells(OECs). Methods:The olfactory nerve layer of adult rat olfactory bulb was dissected. The tissues were minced with a razor blade, and trypsinized using trypsin. OECs were obtained and purified based on their special rate of attachment which was different from the other harvested cell types during culture. DF12 medium supplemented with 10% fetal bovine serum and antibiotics was employed to culture the OECs. Basic fibroblast growth factor (bFGF,20ng/ml) and forskolin (2uM) were added to the medium to enhance OECs growth two days after plating. Half of the medium in each group was refreshed twice a week. OECs were immunocytochemically characterized and confirmed by expression of low-affinity nerve growth factor receptor P75NTR and glial fibrillary acidic protein (GFAP). Results:OECs from the olfactory nerve layer of adult SD rats were highly purified based on the differing rates of attachment of the various cell types. Cultured OECs displayed a typical spindle-shaped soma with long and slim processes. The addition of bFGF and forskolin two days after plating can activate the growth of olfactory ensheathing cells and single layer of OECs was seen seven days after plating.92 percent of the cells cultured were P75NTR immunoreactive, and about 12 percent of the cells positive for GFAP. Conclusion:The high pure of olfactory ensheathing cells could be harvested using special rate of attachment which was different from the other harvested cell types during culture and facilitate the research on the olfactory ensheathing cells in vitro. Addition of basic fibroblast growth factor and forskolin into the medium two days after plating could promote the growth of olfactory ensheathing cells.
Objective: To explore whether olfactory ensheathing cells (OECs) can promote newborn rat spiral ganglion cells (SGCs) survival. Methods:Co-cultures of OECs from adult rat olfactory bulb with SGCs from newborn rat cochlea were established and single culture of SGCs acted as control. In addition, OECs conditioned medium (OEC-CM) was employed to culture SGCs in contrast with the co-cultures. OECs were obtained and purified based on their special rate of attachment which was different from the other harvested cell types during culture. OECs and SGCs were immunocytochemically characterized and confirmed by expression of low-affinity nerve growth factor receptor P75NTR and neuron-specificβⅢ-tubulin, respectively. For statistic analyses, randomized block ANOVA was performed. Results: Single layer of OECs (92% pure) was seen seven days after plating. Surviving SGCs, that extended their primary neurites, were found on the surface of the layer in the co-cultures. When OECs and SGCs were co-cultured, the number of surviving SGCs was significantly greater than that in other two groups (P<0.01). Nine days after culture, there was even no change in the number of surviving SGCs in co-cultures while the number of SGCs in single culture dramatically reduced. The number of surviving SGCs in control group significantly decreased from 14.6±1.1 SGCs/ field on day 3 to 3.3±0.3 SGCs/ field on day 14. By contrast, OEC-CM had a positive effect on SGCs survival, with an overall decrease of surviving SGCs from 35.3±2.1 SGCs/field on day 3 to 12.9±0.3 SGCs/ field on day 14 of culture. Surprisingly, the number of surviving SGCs co-cultured with OECs slightly decreased from 66.9±1.2 SGCs/ field on day 3 to 38.9±1.0 SGCs/ field on day 14. Conclusion:Olfactory ensheathing cells can promote the survival of newborn rat spiral ganglion cell in vitro.
Objective:To explore the underlying mechanisms that OECs promote the survival of SGCs in vitro. Methods:Co-cultures of OECs from adult rat olfactory bulb with SGCs from newborn rat cochlea were established. In the present study, there were three groups:co-cultures, co-cultures with addition of BDNF (500 pg/ml), and co-cultures with addition of anti-BDNF antibody (50μg/ml). The cultures were fixed three days after cultured. SGCs were immunocytochemically characterized and confirmed by the expression of neuron-specificβⅢ-tubulin. One-way ANOVA and Bonferroni were employed to investigate the differences in the number of SGCs in different cultures. Results:In comparison with co-cultures without treatment, addition of BDNF (500 pg/mL) into the medium had no obvious survival-promoting on SGCs. The number of surviving SGCs reduced significantly when anti-BDNF antibody(50μg/mL) was applied into co-cultures (P<0.01). The number of SGCs between co-cultures and co-cultures+BDNF has no significant difference (P>0.05); the difference between co-cultures+anti-BDNF and the others was significant (P<0.01). Conclusion:BDNF expressed by OECs is in part responsible for the survival-promoting of olfactory ensheathing cells on spiral ganglion cells.
目的：纯化培养和鉴定成年大鼠嗅球嗅鞘细胞(olfactory ensheathing cells OECs),为后续实验做好准备。方法：取成年大鼠嗅球神经层,经酶消化的方法获得含有OECs的混合细胞悬液,采用多次长时差速贴壁的方法纯化OECs,用含有10%FBS的DF12培养基培养,2d后培养基中加入bFGF (20ng/ml)和forskolin(2uM)促进OECs的增殖,每隔3d半量更换培养基。倒置相差显微镜下观察OECs的生长状态,采用P75NTR和GFAP细胞免疫组化的方法鉴定OECs,荧光显微镜下观察OECs的形态并统计其纯度。结果：采用多次长时差速贴壁的方法能够去除绝大部分的污染细胞,包括成纤维细胞和星形胶质细胞,接种的OECs约24小时后贴壁,倒置相差显微镜下观察见大部分细胞胞体呈梭形、部分细胞胞体为多角形,伸出突起；细胞在接种培养的前2d生长缓慢,2d后培养基中加入bFGF (20ng/ml)和forskolin(2uM)可见细胞增殖加快,细胞突起细长,培养7d后见OECs覆盖皿底的90%,形成—细胞单层。P75NTR和GFAP染色见约92%的细胞为P75NTR(+),分布在突起、胞体,其中胞核被深染；约12%的细胞为GFAP (+)。结论：采用多次长时差速贴壁的方法能够获得实验所需纯度的OECs,培养基(DF12+10%FBS)中加入bFGF(20ng/ml)和forskolin(2uM)能够显著促进OECs的增殖。
第二部分嗅鞘细胞对耳蜗螺旋神经节细胞离体培养的影响
目的：探索在离体实验中OECs有无促进耳蜗听觉传入神经元—螺旋神经节细胞(spiral ganglion cells SGCs)存活的作用。方法：取成年大鼠嗅球和新生大鼠蜗轴组织块进行OECs与SGCs的培养,采用多次长时差速贴壁的方法纯化培养OECs。实验分OECs与SGCs共培养组、SGCs在OECs条件培养液中(OEC-CM)培养组和SGCs单独培养组。倒置相差显微镜下观察OECs和SGCs生长状态,P75NTR免疫组化法鉴定OECs,神经元特异性标志物βⅢ-tubulin标记SGCs。结果：OECs贴壁培养7天后形成—细胞单层,在OECs与SGCs共培养体系中,SGCs在OECs形成的细胞单层的表面生长,并伸出长突起,呈现典型的双极神经元形态；在培养的前6d,随着培养时间的延长,SGCs较接种前减少,但共培养组中SGCs存活数量明显高于SGCs单独培养组(P<0.01)；与SGCs在OEC-CM中培养比较,共培养组更能促进SGCs存活,并且单独培养组的SGCs数量在培养的第6d出现大幅度减少；在培养的第9d,单独培养组中几乎没有SGCs生长；而在共培养组,SGCs的数量未见明显变化(P>0.05)；统计发现单独培养组中存活的SGCs由第3d的14.6±1.1SGCs/视野(×200)减少到第14d的3.3±0.3SGCs/视野；OEC-CM组中的SGCs由35.3±2.1SGCs/视野下降到12.9±0.3SGCs/视野；共培养组中存活的SGCs较其它组明显增多,由第3d的66.9±1.2SGCs/视野(×200)减少到第14d的38.9×1.0 SGCs/视野。结论：OECs与SGCs共培养能够促进新生大鼠SGCs存活。
第三部分嗅鞘细胞促进螺旋神经节细胞存活的分子机制
目的：初步研究OECs促进SGCs体外存活的分子机制。方法：建立OECs与SGCs共培养体系,实验分三组：共培养+脑源性神经营养因子(BDNF,500 pg/ml)组；共培养+BDNF抗体(IgY型,50 ug/ml)组；对照组为OECs与SGCs共培养。共培养3d后固定,βⅢ-tubulin免疫组化染色鉴定SGCs,每个培养皿随机取4个视野,荧光显微镜下统计βⅢ-tubulin标记的SGCs,统计各培养组中的SGCs。结果：共培养+BDNF组中有大量SGCs在OECs形成的单层细胞毯表面生长,但与对照组比较,SCG的数目无统计学差异；加入BDNF抗体(IgY)的共培养组中的SGCs数量明显减少(P<0.01)。结论：OECs与SGCs共培养中加入BDNF对SGCs存活无明显影响,而加入BDNF抗体(IgY)后存活的SGCs减少。OECs分泌BDNF可能是其促进SGCs体外培养的存活,发挥对SGCs的营养保护作用的分子机制之一。
Part 1 Culture, purification and identification of olfactory ensheathing cells
Objective:To culture and purify olfactory ensheathing cells(OECs). Methods:The olfactory nerve layer of adult rat olfactory bulb was dissected. The tissues were minced with a razor blade, and trypsinized using trypsin. OECs were obtained and purified based on their special rate of attachment which was different from the other harvested cell types during culture. DF12 medium supplemented with 10% fetal bovine serum and antibiotics was employed to culture the OECs. Basic fibroblast growth factor (bFGF,20ng/ml) and forskolin (2uM) were added to the medium to enhance OECs growth two days after plating. Half of the medium in each group was refreshed twice a week. OECs were immunocytochemically characterized and confirmed by expression of low-affinity nerve growth factor receptor P75NTR and glial fibrillary acidic protein (GFAP). Results:OECs from the olfactory nerve layer of adult SD rats were highly purified based on the differing rates of attachment of the various cell types. Cultured OECs displayed a typical spindle-shaped soma with long and slim processes. The addition of bFGF and forskolin two days after plating can activate the growth of olfactory ensheathing cells and single layer of OECs was seen seven days after plating.92 percent of the cells cultured were P75NTR immunoreactive, and about 12 percent of the cells positive for GFAP. Conclusion:The high pure of olfactory ensheathing cells could be harvested using special rate of attachment which was different from the other harvested cell types during culture and facilitate the research on the olfactory ensheathing cells in vitro. Addition of basic fibroblast growth factor and forskolin into the medium two days after plating could promote the growth of olfactory ensheathing cells.
Objective: To explore whether olfactory ensheathing cells (OECs) can promote newborn rat spiral ganglion cells (SGCs) survival. Methods:Co-cultures of OECs from adult rat olfactory bulb with SGCs from newborn rat cochlea were established and single culture of SGCs acted as control. In addition, OECs conditioned medium (OEC-CM) was employed to culture SGCs in contrast with the co-cultures. OECs were obtained and purified based on their special rate of attachment which was different from the other harvested cell types during culture. OECs and SGCs were immunocytochemically characterized and confirmed by expression of low-affinity nerve growth factor receptor P75NTR and neuron-specificβⅢ-tubulin, respectively. For statistic analyses, randomized block ANOVA was performed. Results: Single layer of OECs (92% pure) was seen seven days after plating. Surviving SGCs, that extended their primary neurites, were found on the surface of the layer in the co-cultures. When OECs and SGCs were co-cultured, the number of surviving SGCs was significantly greater than that in other two groups (P<0.01). Nine days after culture, there was even no change in the number of surviving SGCs in co-cultures while the number of SGCs in single culture dramatically reduced. The number of surviving SGCs in control group significantly decreased from 14.6±1.1 SGCs/ field on day 3 to 3.3±0.3 SGCs/ field on day 14. By contrast, OEC-CM had a positive effect on SGCs survival, with an overall decrease of surviving SGCs from 35.3±2.1 SGCs/field on day 3 to 12.9±0.3 SGCs/ field on day 14 of culture. Surprisingly, the number of surviving SGCs co-cultured with OECs slightly decreased from 66.9±1.2 SGCs/ field on day 3 to 38.9±1.0 SGCs/ field on day 14. Conclusion:Olfactory ensheathing cells can promote the survival of newborn rat spiral ganglion cell in vitro.
Objective:To explore the underlying mechanisms that OECs promote the survival of SGCs in vitro. Methods:Co-cultures of OECs from adult rat olfactory bulb with SGCs from newborn rat cochlea were established. In the present study, there were three groups:co-cultures, co-cultures with addition of BDNF (500 pg/ml), and co-cultures with addition of anti-BDNF antibody (50μg/ml). The cultures were fixed three days after cultured. SGCs were immunocytochemically characterized and confirmed by the expression of neuron-specificβⅢ-tubulin. One-way ANOVA and Bonferroni were employed to investigate the differences in the number of SGCs in different cultures. Results:In comparison with co-cultures without treatment, addition of BDNF (500 pg/mL) into the medium had no obvious survival-promoting on SGCs. The number of surviving SGCs reduced significantly when anti-BDNF antibody(50μg/mL) was applied into co-cultures (P<0.01). The number of SGCs between co-cultures and co-cultures+BDNF has no significant difference (P>0.05); the difference between co-cultures+anti-BDNF and the others was significant (P<0.01). Conclusion:BDNF expressed by OECs is in part responsible for the survival-promoting of olfactory ensheathing cells on spiral ganglion cells.
引文
1. Aayesha M Khan,Ophir Handzel,Doris Damian,Donald K Eddington,Joseph B Nadol Jr. Effect of cochlear implantation on residual spiral ganglion cell count as determined by comparison with the contralateral nonimplanted inner ear in humans. Ann. Otol. Rhinol. Laryngol.2005;114:381-385.
2. Nadol J.B.Jr, Yi-Shyang Yong, Glynn R.J.1989. Survival of spiral ganglion cells in profound sensorineural hearing loss:implications for cochlear implantation. Ann. Otol. Rhinol. Laryngol.1989; 98:411-416.
3. Robert K.Shepherd, Eric Javel. Electrical stimulation of the auditory nerve.Ⅰ. Correlation of physiological responses with cochlear status. Hear Res 1997; 108:112-144.
4. Lisa N.Gillespie, Graeme M.Clark, Perry F.Bartlett, et al. BDNF-induced survival of auditory neurons in vivo:cessation of treatment leads to an accelerated loss of survival effects. Neurosci Res 2003; 71:785-790.
5. Iguchi F, Nakagawa T, Tateya I, Kim TS, Endo T, Taniguchi Z, Naito Y, Ito J. Trophic support of mouse inner ear by neural stem cell transplantation. Neuroreport. 2003;20:14(1):77-80.
6. Mark A. Parker, Deborah A. Corliss, Brianna Gray, Julia K. Anderson, Richard P. Bobbin, Evan Y. Snyder, Douglas A. Cotanche. Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hearing Research 232 (2007) 29-43.
7. Catania S, Germana A, Cabo R, Ochoa-Erena FJ, Guerrera MC, Hannestad J, Represa J, Vega JA. Neurotrophin and Trk neurotrophin receptors in the inner ear of Salmo salar and Salmo trutta. J Anat 2007; 210(1):78-88.
8. Hossain WA, D'Sa C, Morest DK. Interactive roles of fibroblast growth factor 2 and neurotrophin 3 in the sequence of migration, process outgrowth, and axonal differentiation of mouse cochlear ganglion cells. J Neurosci Res.2008; 86(11):2376-2391.
9. Sun W, Salvi RJ. Brain derived neurotrophic factor and neurotrophic factor 3 modulate neurotransmitter receptor expressions on developing spiral ganglion neurons. Neuroscience.2009; 164(4):1854-1866.
10. Ulla Pirvola,Urmas Arumae, Maxim Moshnyakov,et al. Coordinated expression and function of neurotrophins and their receptors in the rat inner ear during target innervation. Hear. Res.1994; 75:131-144.
11. Wheeler E.F., Bothwell M., Schecterson L.C.& von Bartheld, C.S. Expression of BDNF and NT-3 mRNA in hair cells of the organ of Corti:quantitative analysis in developing rats. Hear. Res.1994;73:46-56.
12.刁明芳,高文元,孙建军.等.一氧化氮合酶抑制剂和神经营养因子3对噪声暴露下豚鼠耳蜗的保护作用.中华耳鼻咽喉头颈外科杂志.2007,42(4)：281-285.
13. Rachael T. Richardson, Stephen O'Leary, Andrew Wise, et al. A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support. Hear Res.2005;204:37-47.
14. Andrew K.Wise, Rachael Richardso,Jennifer Hardman, et al. Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3. J. Comp. Neurol.2005;487:147-165.
15. Staecker H,Gabaizeadeh R,Federoff H,et al. Brain-drived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss. J.Otolaryngol Head Neck Surgery,1998;119:7-13.
16.邓志宏,王锦玲,邱建华等.阳离子脂质体介导NT-3基因转染豚鼠耳蜗的实验研究。听力学及言语疾病杂志,2004；(12)：182-184.
17. Chuah MI, Au C. Cultures of ensheathing cells from neonatal rat olfactory bulbs. Brain Res.1993;601(1-2):213-220.
18. Lipson AC, Widenfalk J, Lindqvist E, Ebendal T, Olson L. Neurotrophic properties of olfactory ensheathing glia. Exp Neurol 2003; 180(2):167-171.
19. Woodhall E, West AK, Chuah MI. Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors. Brain Res Mol Brain Res. 2001;88(1-2):203-213.
20. Christine Radtke, Ayal A.Aizer, Samuel K.Agulian, et al. Transplantion of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair. J Brain Research,2009; 1254:10-17.
21. Geoff Raisman. Olfactory ensheathing cells-another miracle cure and for spinal cord injure. Nat Rev Neurosci.2001;2(5):369-374
22. Radtke, C., et al. Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury. J Rehabil Res Dev,2008;45(1):141-51.
23. Li Y, Sauve Y, Li D, Lund RD, Raisman G. Transplanted olfactory ensheathing cells promote regeneration of cut adult rat optic nerve axons. J Neurosci 2003; 23(21): 7783-7788.
24. Lund R, Budko E, Lu B, et al. Assessment of Olfactory Ensheathing Cells as a Cell-Based Therapy to Prevent Photoreceptor Degeneration in the Royal College of Surgeons Rat. Invest Ophthalmol Vis Sci,2005;46:1653-1661.
25. Pastrana E, Moreno-Flores MT, Avila J, Wandosell F, Minichiello L, Diaz-Nido J. BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons. Neurochem Int 2007; 50(3):491-498.
26. Ramo'n-Cueto A, Nieto-Sampedro M. Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol 1994; 127:232-244.
27. Gudino-Cabrera G, Nieto-Sampedro M. Ensheathing cells:large scale purification from adult olfactory bulb, freeze preservation and migration of transplanted cells in adult brain. Restor Neurol Neurosci 1996; 10:25-34.
28. Almudena Ramo'n-Cueto and Jesu's Avila. Olfactory ensheathing glia: Properties and function. Brain Research Bulletin,1998;46(3):175-187.
29. Doucette, R. Glial progenitor cells of the nerve fiber layer of the olfactory bulb: Effect of astrocyte growth media. J. Neurosci. Res.1993;35:274-287.
30. Goodman, M. N., Silver, J., Jacobberger, J. W. Establishment and neurite outgrowth properties of neonatal and adult rat olfactory bulb glial cell lines. Brain Res.1993;619:199-213.
31. Pixley, S. K. Characteristics of olfactory receptor neurons and other cell types in dissociated rat olfactory cell cultures. Int. J. Dev. Neurosci.1996;14:823-839.
32. Nash HH, Borke RC, Anders JJ. New method of purification for establishing primary cultures of ensheathing cells from the adult olfactory bulb. Glia 2001; 34(2): 81-87.
33. Chuah MI, Teague R. Basic fibroblast growth factor in the primary olfactory pathway:mitogenic effect on ensheathing cells. Neuroscience 1999; 88(4): 1043-1050.
34. Ramon-Cueto, A., Nieto-Sampedro, M. Glial cells from the adult rat olfactory bulb:Immunocytochemical properties of pure cultures of ensheathing cells. Neurosci.1992;47:213-220.
35. Ramo'n-Cueto, A., Pe'rez, J.,Nieto-Sampedro, M. In vitro enfolding of olfactory neurites by p75 NGF receptor positive ensheathing cells from adult rat olfactory bulb. Eur. J. Neurosci.1993;5:1172-1180.
36. Rolland B., Le Prince G., Fages C., Nunez J. and Tardy M. GFAP turnover during astroglial proliferation and differentiation. Devl Brain Res,1990;56:144-149.
37. Zhang YM, Ma B, Gao WY, Wen W, Liu HY. Role of glutamate receptors in the spiral ganglion neuron damage induced by acoustic noise. Acta Physiol Sin.2007; 59 (1):103-110.
38. Yu XD, Luo ZJ, Zhang L, Gong K. Effects of olfactory ensheathing cells on hydrogen peroxide-induced apoptosis in cultured dorsal root ganglion neurons. Chin Med J (Engl).2007;120(16):1438-1443.
39. Feng L, Meng H, Wu F, Cheng B, He X, Wang X, Li Z, Liu S. Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC 12 cells through modulation of intrinsic apoptotic pathways. Int J Dev Neurosci. 2008;26(3-4):323-329.
40. Srivastava N, Seth K, Khanna VK, Ansari RW, Agrawal AK. Long-term functional restoration by neural progenitor cell transplantation in rat model of cognitive dysfunction:co-transplantation with olfactory ensheathing cells for neurotrophic factor support. Int J Dev Neurosci.2009;27(1):103-110.
41. Pellitteri R, Spatuzza M, Russo A, Stanzani S. Olfactory ensheathing cells exert a trophic effect on the hypothalamic neurons in vitro. Neurosci Lett. 2007;417(1):24-29.
42. Ylikoski, J., Pirvola, U., Moshnyakov, M., Palgi, J., Arumae, U. Saarma, M. Expression patterns of neurotrophin and their receptor mRNAs in the rat inner ear. Hear.Res.1993;65:69-78.
43. Hossain, W.A.& Morest, D.K. Fibroblast growth factors (FGF-1, FGF-2) promote migration and neurite growth of mouse cochlear ganglion cells in vitro: immunohistochemistry and antibody perturbation. J. Neurosci. Res.2000; 62:40-55.
44. Mueller, K.L., Jacques, B.E.& Kelley, M.W. Fibroblast growth factor signaling regulates pillar cell development in the organ of corti. J. Neurosci.2002; 22:9368-9377.
45. Miller, J.M., Le Prell, C.G., Prieskorn, D.M., Wys, N.L., Altschuler, R.A. Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes:effects of brain-derived neurotrophic factor and fibroblast growth factor. J. Neurosci. Res.2007; 85:1959-1969.
46. Glueckert R., Bitsche M., Miller J.M., Zhu Y., Prieskorn D.M., Altschuler R.A., Schrott-Fischer A. Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor. J. Comp. Neurol.2008;507:1602-1621.
47. Martijn J.H. Agterberg, Huib Versnel, John C.M.J. de Groot, Guido F. Smoorenburg, Frans W.J. Albers, Sjaak F.L. Klis. Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs. Hearing Res.2008;244:25-34.
48.布林,钟环,姜汉国。NGF、BDNF基因修饰嗅鞘细胞脊髓内移植对损伤脊髓细胞的保护作用。中国矫形外科杂志,2003；11(18)：1277-1278.
49. Marc J.Ruitenberg, Giles W.Plant,Frank P.Hamers,et al. Ex vivo adenoviral vector-mediated neurotrophin gene transfer to olfactory ensheathing glia:effects on rubrospinal tract regeneration,lesion size,and functional recovery after implantion in the injured rat spinal cord J Neurosci,2003,23:7045-7058.
50. Jing Ye, Huawei Li, Hongmeng Yu, Jian Zhang, Hongqun Jiang, Chunfu Dai. Conditioned medium from neonatal rat olfactory ensheathing cells promotes the survival and proliferation of spiral ganglion cells. Acta Otolaryngol 2009; 25:1-7.
51. Kimura K, Matsumoto N, Kitada M, Mizoguchi A, Ide C. Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro. J Neurocytol 2004;33(4):465-476.
52. Deumens R, Koopmans GC, Den Bakker CG, Maquet V, Blacher S, Honig WM, Jerome R, Pirard JP, Steinbusch HW, Joosten EA. Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro. Neuroscience 2004;125(3):591-604.
53. Miller JM, Chi DH, O'Keeffe LJ, Kruszka P, Raphael Y, Altschuler RA. Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss. Int J Dev Neurosci 1997; 15(4-5):631-643.
54. Agterberg MJ, Versnel H, van Dijk LM, de Groot JC, Klis SF. Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs. J Assoc Res Otolaryngol 2009; 10(3): 355-367.
[1]Cowan, C.M., Roskams, A.J. Apoptosis in the mature and developing olfactory neuroepithelium[J]. Microsc. Res. Tech.2002, (58):204-215.
[2]Vincent, A.J., Taylor, J.M., Choi-Lundberg, D.L.et al. Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes[J]. Glia,2005,51 (2):132-147.
[3]Lopez-Vales, R., Fores, J., Verdu, E. et al. Acute and delayed transplantation of olfactory ensheathing cells promote partial recovery after complete transection of the spinal cord[J]. Neurobiol. Dis.2006, (21):57-68.
[4]Li, Y., Carlstedt, T., Berthold, C.H.et al. Interaction of transplanted olfactory-ensheathing cells and host astrocytic processes provides a bridge for axons to regenerate across the dorsal root entry zone[J]. Exp. Neurol,2004(188):300-308.
[5]Lipson, A.C., Widenfalk, J., Lindqvist, E.et al. Neurotrophic properties of olfactory ensheathing glia[J]. Exp. Neurol,2003, (180):167-171.
[6]KARL W. KAFITZ AND CHARLES A. GREER. Olfactory Ensheathing Cells Promote Neurite Extension from Embryonic Olfactory Receptor Cells In Vitro[J]. GLIA,1999,25(2):99-110.
[7]Wu, M.M., et al. Death of Axotomized Retinal Ganglion Cells Delayed after Intraoptic Nerve Transplantation of Olfactory Ensheathing Cells in Adult Rats. Cell Transplant,2010. [Epub ahead of print]
[8]RAKESH J. SONIGRA, PHILIP C. Adult Rat Olfactory Nerve Ensheathing Cells Are Effective Promoters of Adult Central Nervous System Neurite Outgrowth in Coculture[J]. GLIA,1999,25(3):256-269.
[9]ROHAN KUMAR, CAROLINE WIGLEY. Functional Differences and Interactions Between Phenotypic Subpopulations of Olfactory Ensheathing Cells in Promoting CNS Axonal Regeneration[J]. GLIA,2005,50(1):12-20.
[10]Shukla, S., et al., Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonian rats. J Neurochem,2009.109(2):436-451.
[11]Pellitteri, R., et al., Olfactory ensheathing cells represent an optimal substrate for hippocampal neurons:an in vitro study. Int J Dev Neurosci,2009.27(5):453-458.
[12]Lopez-Vales, R. et al. Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat. Glia,2007. 55(3):303-311.
[13]Y. Li, P. Decherchi, G. Raisman. Transplantation of olfactory ensheathing cells into spinal cord lesions restores breathing and climbing [J]. Neurosci.2003,23(3): 727-731.
[14]Geoffrey Raisman. Repair of spinal cord injury by transplantation of olfactory ensheathing cells[J]. C. R. Biologies,2007,330(6-7):557-560.
[15]Van Den Pol, A.N., Santarelli, J.G. Olfactory ensheathing cells:time lapse imaging of cellular interactions, axonal support, rapid morphologic shifts, and mitosis[J]. Comp. Neurol.2003, (458):175-194.
[16]Emma Woodhall, Adrian K. Molecular. Cultured olfactory ensheathing cells express nerve growth factor,brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors[J]. Brain Research,2001,88(1-2):203-213
[17]Jing Ye, Huawei Li, Hongmeng Yu, Jian Zhang, Hongqun Jiang, Chunfu Dai. Conditioned medium from neonatal rat olfactory ensheathing cells promotes the survival and proliferation of spiral ganglion cells. Acta Otolaryngol 2009; 25:1-7.
[18]Erika Pastrana, Maria Teresa Moreno-Flores. BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons[J]. Neurochemistry International,2007,50(3):491-498.
[19]Silvio Rizzoli, Geeta Sharma, Sukumar Vijayaraghavan. Calcium rise in cultured neurons from medial septum elicits calcium waves in surrounding glial cells[J]. Brain Research,2002,957(2):287-297.
[20]ANNE R, JOACHIMW D, et al. Axon-Glia Communication Evokes Calcium Signaling in Olfactory Ensheathing Cells of the Developing Olfactory Bulb[J]. GLIA,2007,55(4):352-359.
[21]Hayat S,Wigley CB, Robbins J. Intracellular calcium handling in rat olfactory ensheathing cells and its role in axonal regeneration[J]. Mol Cell Neurosci,2003, 22(2):259-270.
[22]SHAISTA HAYAT, CAROLINE B. WIGLEY. Manipulation of Olfactory Ensheathing Cell Signaling Mechanisms:Effects on Their Support for Neurite Regrowth From Adult CNS Neurons in Coculture[J]. GLIA,2003,44(3):232-241.
2. Nadol J.B.Jr, Yi-Shyang Yong, Glynn R.J.1989. Survival of spiral ganglion cells in profound sensorineural hearing loss:implications for cochlear implantation. Ann. Otol. Rhinol. Laryngol.1989; 98:411-416.
3. Robert K.Shepherd, Eric Javel. Electrical stimulation of the auditory nerve.Ⅰ. Correlation of physiological responses with cochlear status. Hear Res 1997; 108:112-144.
4. Lisa N.Gillespie, Graeme M.Clark, Perry F.Bartlett, et al. BDNF-induced survival of auditory neurons in vivo:cessation of treatment leads to an accelerated loss of survival effects. Neurosci Res 2003; 71:785-790.
5. Iguchi F, Nakagawa T, Tateya I, Kim TS, Endo T, Taniguchi Z, Naito Y, Ito J. Trophic support of mouse inner ear by neural stem cell transplantation. Neuroreport. 2003;20:14(1):77-80.
6. Mark A. Parker, Deborah A. Corliss, Brianna Gray, Julia K. Anderson, Richard P. Bobbin, Evan Y. Snyder, Douglas A. Cotanche. Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hearing Research 232 (2007) 29-43.
7. Catania S, Germana A, Cabo R, Ochoa-Erena FJ, Guerrera MC, Hannestad J, Represa J, Vega JA. Neurotrophin and Trk neurotrophin receptors in the inner ear of Salmo salar and Salmo trutta. J Anat 2007; 210(1):78-88.
8. Hossain WA, D'Sa C, Morest DK. Interactive roles of fibroblast growth factor 2 and neurotrophin 3 in the sequence of migration, process outgrowth, and axonal differentiation of mouse cochlear ganglion cells. J Neurosci Res.2008; 86(11):2376-2391.
9. Sun W, Salvi RJ. Brain derived neurotrophic factor and neurotrophic factor 3 modulate neurotransmitter receptor expressions on developing spiral ganglion neurons. Neuroscience.2009; 164(4):1854-1866.
10. Ulla Pirvola,Urmas Arumae, Maxim Moshnyakov,et al. Coordinated expression and function of neurotrophins and their receptors in the rat inner ear during target innervation. Hear. Res.1994; 75:131-144.
11. Wheeler E.F., Bothwell M., Schecterson L.C.& von Bartheld, C.S. Expression of BDNF and NT-3 mRNA in hair cells of the organ of Corti:quantitative analysis in developing rats. Hear. Res.1994;73:46-56.
12.刁明芳,高文元,孙建军.等.一氧化氮合酶抑制剂和神经营养因子3对噪声暴露下豚鼠耳蜗的保护作用.中华耳鼻咽喉头颈外科杂志.2007,42(4)：281-285.
13. Rachael T. Richardson, Stephen O'Leary, Andrew Wise, et al. A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support. Hear Res.2005;204:37-47.
14. Andrew K.Wise, Rachael Richardso,Jennifer Hardman, et al. Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3. J. Comp. Neurol.2005;487:147-165.
15. Staecker H,Gabaizeadeh R,Federoff H,et al. Brain-drived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss. J.Otolaryngol Head Neck Surgery,1998;119:7-13.
16.邓志宏,王锦玲,邱建华等.阳离子脂质体介导NT-3基因转染豚鼠耳蜗的实验研究。听力学及言语疾病杂志,2004；(12)：182-184.
17. Chuah MI, Au C. Cultures of ensheathing cells from neonatal rat olfactory bulbs. Brain Res.1993;601(1-2):213-220.
18. Lipson AC, Widenfalk J, Lindqvist E, Ebendal T, Olson L. Neurotrophic properties of olfactory ensheathing glia. Exp Neurol 2003; 180(2):167-171.
19. Woodhall E, West AK, Chuah MI. Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors. Brain Res Mol Brain Res. 2001;88(1-2):203-213.
20. Christine Radtke, Ayal A.Aizer, Samuel K.Agulian, et al. Transplantion of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair. J Brain Research,2009; 1254:10-17.
21. Geoff Raisman. Olfactory ensheathing cells-another miracle cure and for spinal cord injure. Nat Rev Neurosci.2001;2(5):369-374
22. Radtke, C., et al. Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury. J Rehabil Res Dev,2008;45(1):141-51.
23. Li Y, Sauve Y, Li D, Lund RD, Raisman G. Transplanted olfactory ensheathing cells promote regeneration of cut adult rat optic nerve axons. J Neurosci 2003; 23(21): 7783-7788.
24. Lund R, Budko E, Lu B, et al. Assessment of Olfactory Ensheathing Cells as a Cell-Based Therapy to Prevent Photoreceptor Degeneration in the Royal College of Surgeons Rat. Invest Ophthalmol Vis Sci,2005;46:1653-1661.
25. Pastrana E, Moreno-Flores MT, Avila J, Wandosell F, Minichiello L, Diaz-Nido J. BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons. Neurochem Int 2007; 50(3):491-498.
26. Ramo'n-Cueto A, Nieto-Sampedro M. Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol 1994; 127:232-244.
27. Gudino-Cabrera G, Nieto-Sampedro M. Ensheathing cells:large scale purification from adult olfactory bulb, freeze preservation and migration of transplanted cells in adult brain. Restor Neurol Neurosci 1996; 10:25-34.
28. Almudena Ramo'n-Cueto and Jesu's Avila. Olfactory ensheathing glia: Properties and function. Brain Research Bulletin,1998;46(3):175-187.
29. Doucette, R. Glial progenitor cells of the nerve fiber layer of the olfactory bulb: Effect of astrocyte growth media. J. Neurosci. Res.1993;35:274-287.
30. Goodman, M. N., Silver, J., Jacobberger, J. W. Establishment and neurite outgrowth properties of neonatal and adult rat olfactory bulb glial cell lines. Brain Res.1993;619:199-213.
31. Pixley, S. K. Characteristics of olfactory receptor neurons and other cell types in dissociated rat olfactory cell cultures. Int. J. Dev. Neurosci.1996;14:823-839.
32. Nash HH, Borke RC, Anders JJ. New method of purification for establishing primary cultures of ensheathing cells from the adult olfactory bulb. Glia 2001; 34(2): 81-87.
33. Chuah MI, Teague R. Basic fibroblast growth factor in the primary olfactory pathway:mitogenic effect on ensheathing cells. Neuroscience 1999; 88(4): 1043-1050.
34. Ramon-Cueto, A., Nieto-Sampedro, M. Glial cells from the adult rat olfactory bulb:Immunocytochemical properties of pure cultures of ensheathing cells. Neurosci.1992;47:213-220.
35. Ramo'n-Cueto, A., Pe'rez, J.,Nieto-Sampedro, M. In vitro enfolding of olfactory neurites by p75 NGF receptor positive ensheathing cells from adult rat olfactory bulb. Eur. J. Neurosci.1993;5:1172-1180.
36. Rolland B., Le Prince G., Fages C., Nunez J. and Tardy M. GFAP turnover during astroglial proliferation and differentiation. Devl Brain Res,1990;56:144-149.
37. Zhang YM, Ma B, Gao WY, Wen W, Liu HY. Role of glutamate receptors in the spiral ganglion neuron damage induced by acoustic noise. Acta Physiol Sin.2007; 59 (1):103-110.
38. Yu XD, Luo ZJ, Zhang L, Gong K. Effects of olfactory ensheathing cells on hydrogen peroxide-induced apoptosis in cultured dorsal root ganglion neurons. Chin Med J (Engl).2007;120(16):1438-1443.
39. Feng L, Meng H, Wu F, Cheng B, He X, Wang X, Li Z, Liu S. Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC 12 cells through modulation of intrinsic apoptotic pathways. Int J Dev Neurosci. 2008;26(3-4):323-329.
40. Srivastava N, Seth K, Khanna VK, Ansari RW, Agrawal AK. Long-term functional restoration by neural progenitor cell transplantation in rat model of cognitive dysfunction:co-transplantation with olfactory ensheathing cells for neurotrophic factor support. Int J Dev Neurosci.2009;27(1):103-110.
41. Pellitteri R, Spatuzza M, Russo A, Stanzani S. Olfactory ensheathing cells exert a trophic effect on the hypothalamic neurons in vitro. Neurosci Lett. 2007;417(1):24-29.
42. Ylikoski, J., Pirvola, U., Moshnyakov, M., Palgi, J., Arumae, U. Saarma, M. Expression patterns of neurotrophin and their receptor mRNAs in the rat inner ear. Hear.Res.1993;65:69-78.
43. Hossain, W.A.& Morest, D.K. Fibroblast growth factors (FGF-1, FGF-2) promote migration and neurite growth of mouse cochlear ganglion cells in vitro: immunohistochemistry and antibody perturbation. J. Neurosci. Res.2000; 62:40-55.
44. Mueller, K.L., Jacques, B.E.& Kelley, M.W. Fibroblast growth factor signaling regulates pillar cell development in the organ of corti. J. Neurosci.2002; 22:9368-9377.
45. Miller, J.M., Le Prell, C.G., Prieskorn, D.M., Wys, N.L., Altschuler, R.A. Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes:effects of brain-derived neurotrophic factor and fibroblast growth factor. J. Neurosci. Res.2007; 85:1959-1969.
46. Glueckert R., Bitsche M., Miller J.M., Zhu Y., Prieskorn D.M., Altschuler R.A., Schrott-Fischer A. Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor. J. Comp. Neurol.2008;507:1602-1621.
47. Martijn J.H. Agterberg, Huib Versnel, John C.M.J. de Groot, Guido F. Smoorenburg, Frans W.J. Albers, Sjaak F.L. Klis. Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs. Hearing Res.2008;244:25-34.
48.布林,钟环,姜汉国。NGF、BDNF基因修饰嗅鞘细胞脊髓内移植对损伤脊髓细胞的保护作用。中国矫形外科杂志,2003；11(18)：1277-1278.
49. Marc J.Ruitenberg, Giles W.Plant,Frank P.Hamers,et al. Ex vivo adenoviral vector-mediated neurotrophin gene transfer to olfactory ensheathing glia:effects on rubrospinal tract regeneration,lesion size,and functional recovery after implantion in the injured rat spinal cord J Neurosci,2003,23:7045-7058.
50. Jing Ye, Huawei Li, Hongmeng Yu, Jian Zhang, Hongqun Jiang, Chunfu Dai. Conditioned medium from neonatal rat olfactory ensheathing cells promotes the survival and proliferation of spiral ganglion cells. Acta Otolaryngol 2009; 25:1-7.
51. Kimura K, Matsumoto N, Kitada M, Mizoguchi A, Ide C. Neurite outgrowth from hippocampal neurons is promoted by choroid plexus ependymal cells in vitro. J Neurocytol 2004;33(4):465-476.
52. Deumens R, Koopmans GC, Den Bakker CG, Maquet V, Blacher S, Honig WM, Jerome R, Pirard JP, Steinbusch HW, Joosten EA. Alignment of glial cells stimulates directional neurite growth of CNS neurons in vitro. Neuroscience 2004;125(3):591-604.
53. Miller JM, Chi DH, O'Keeffe LJ, Kruszka P, Raphael Y, Altschuler RA. Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss. Int J Dev Neurosci 1997; 15(4-5):631-643.
54. Agterberg MJ, Versnel H, van Dijk LM, de Groot JC, Klis SF. Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs. J Assoc Res Otolaryngol 2009; 10(3): 355-367.
[1]Cowan, C.M., Roskams, A.J. Apoptosis in the mature and developing olfactory neuroepithelium[J]. Microsc. Res. Tech.2002, (58):204-215.
[2]Vincent, A.J., Taylor, J.M., Choi-Lundberg, D.L.et al. Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes[J]. Glia,2005,51 (2):132-147.
[3]Lopez-Vales, R., Fores, J., Verdu, E. et al. Acute and delayed transplantation of olfactory ensheathing cells promote partial recovery after complete transection of the spinal cord[J]. Neurobiol. Dis.2006, (21):57-68.
[4]Li, Y., Carlstedt, T., Berthold, C.H.et al. Interaction of transplanted olfactory-ensheathing cells and host astrocytic processes provides a bridge for axons to regenerate across the dorsal root entry zone[J]. Exp. Neurol,2004(188):300-308.
[5]Lipson, A.C., Widenfalk, J., Lindqvist, E.et al. Neurotrophic properties of olfactory ensheathing glia[J]. Exp. Neurol,2003, (180):167-171.
[6]KARL W. KAFITZ AND CHARLES A. GREER. Olfactory Ensheathing Cells Promote Neurite Extension from Embryonic Olfactory Receptor Cells In Vitro[J]. GLIA,1999,25(2):99-110.
[7]Wu, M.M., et al. Death of Axotomized Retinal Ganglion Cells Delayed after Intraoptic Nerve Transplantation of Olfactory Ensheathing Cells in Adult Rats. Cell Transplant,2010. [Epub ahead of print]
[8]RAKESH J. SONIGRA, PHILIP C. Adult Rat Olfactory Nerve Ensheathing Cells Are Effective Promoters of Adult Central Nervous System Neurite Outgrowth in Coculture[J]. GLIA,1999,25(3):256-269.
[9]ROHAN KUMAR, CAROLINE WIGLEY. Functional Differences and Interactions Between Phenotypic Subpopulations of Olfactory Ensheathing Cells in Promoting CNS Axonal Regeneration[J]. GLIA,2005,50(1):12-20.
[10]Shukla, S., et al., Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonian rats. J Neurochem,2009.109(2):436-451.
[11]Pellitteri, R., et al., Olfactory ensheathing cells represent an optimal substrate for hippocampal neurons:an in vitro study. Int J Dev Neurosci,2009.27(5):453-458.
[12]Lopez-Vales, R. et al. Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat. Glia,2007. 55(3):303-311.
[13]Y. Li, P. Decherchi, G. Raisman. Transplantation of olfactory ensheathing cells into spinal cord lesions restores breathing and climbing [J]. Neurosci.2003,23(3): 727-731.
[14]Geoffrey Raisman. Repair of spinal cord injury by transplantation of olfactory ensheathing cells[J]. C. R. Biologies,2007,330(6-7):557-560.
[15]Van Den Pol, A.N., Santarelli, J.G. Olfactory ensheathing cells:time lapse imaging of cellular interactions, axonal support, rapid morphologic shifts, and mitosis[J]. Comp. Neurol.2003, (458):175-194.
[16]Emma Woodhall, Adrian K. Molecular. Cultured olfactory ensheathing cells express nerve growth factor,brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors[J]. Brain Research,2001,88(1-2):203-213
[17]Jing Ye, Huawei Li, Hongmeng Yu, Jian Zhang, Hongqun Jiang, Chunfu Dai. Conditioned medium from neonatal rat olfactory ensheathing cells promotes the survival and proliferation of spiral ganglion cells. Acta Otolaryngol 2009; 25:1-7.
[18]Erika Pastrana, Maria Teresa Moreno-Flores. BDNF production by olfactory ensheathing cells contributes to axonal regeneration of cultured adult CNS neurons[J]. Neurochemistry International,2007,50(3):491-498.
[19]Silvio Rizzoli, Geeta Sharma, Sukumar Vijayaraghavan. Calcium rise in cultured neurons from medial septum elicits calcium waves in surrounding glial cells[J]. Brain Research,2002,957(2):287-297.
[20]ANNE R, JOACHIMW D, et al. Axon-Glia Communication Evokes Calcium Signaling in Olfactory Ensheathing Cells of the Developing Olfactory Bulb[J]. GLIA,2007,55(4):352-359.
[21]Hayat S,Wigley CB, Robbins J. Intracellular calcium handling in rat olfactory ensheathing cells and its role in axonal regeneration[J]. Mol Cell Neurosci,2003, 22(2):259-270.
[22]SHAISTA HAYAT, CAROLINE B. WIGLEY. Manipulation of Olfactory Ensheathing Cell Signaling Mechanisms:Effects on Their Support for Neurite Regrowth From Adult CNS Neurons in Coculture[J]. GLIA,2003,44(3):232-241.