Regeneration of human auditory nerve.: In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion

Regeneration of human auditory nerve.: In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion
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DOI:
10.1016/j.heares.2004.12.005
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发表时间:
2005-05-01
期刊:
影响因子:
2.8
通讯作者:
Lindholm, D
Lindholm, D
中科院分区:
医学1区
文献类型:
--
作者:
Rask-Andersen, H;Boström, M;Lindholm, D

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培养的成年人和豚鼠螺旋神经节(hSG和gpSG)的延时录像显示,有丝分裂原反应祖细胞/干细胞以球体的形式发育,增殖并分化为成熟的神经元和神经胶质细胞。EGF和bFGF培养的神经球显示巢蛋白的表达和5 '-溴-2-脱氧尿苷(BrdU)的掺入。新形成的BrdU标记的细胞对β-微管蛋白呈阳性,并且对GFAP也呈阳性,表明神经元细胞来源于分裂的祖细胞群体。与胶质细胞系源性神经营养因子(GDNF)或脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)一起培养的解离球诱导祖细胞的分化。视频显微镜显示,神经元从维持长达四周的传代培养球中发育。神经元以10-30 μ m/h的速度成束和迁移,并且一些细胞具有长达6 mm的共表达TrkB和TrkC受体的神经突。精确的解剖表明,形成的神经元是耳蜗特异性的。结果表明,哺乳动物听神经具有自我更新和替代的能力。祖细胞移植与既定的手段,以诱导神经分化和纤维生长,可能有助于更好地修复和治疗听觉神经元损伤的策略。(c)2004 Elsevier B. V.保留所有权利。
Time lapse video recordings of cultured adult human and guinea pig spiral ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells develop in the form of spheres that proliferate and differentiate into mature neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed expression of nestin and incorporation of 5 '-Bromo-2-deoxyuridine (BrdU). Newly formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP demonstrating that neuronal cells were derived from a dividing population of progenitor cells. Dissociated spheres cultured either with glia cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video microscopy showed that neurons develop from subcultured spheres maintained for up to four weeks. Neurons showed fasciculation and migration with a speed of 10-30 mu m/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC receptors. Precise dissection suggests that the neurons formed are cochlea-specific. The results suggest that the mammalian auditory nerve has the capability for self-renewal and replacement. Transplantation of progenitor cells together with established means to induce neural differentiation and fiber growth may facilitate strategies for better repair and treatment of auditory neuronal damage. (c) 2004 Elsevier B.V. All rights reserved.