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Transplantation of Mouse Embryonic Stem Cells into the Cochlea of an Auditory-Neuropathy Animal Model: Effects of Timing after Injury

机译:小鼠胚胎干细胞移植入听觉神经病动物模型的耳蜗:损伤后时间的影响。

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摘要

Application of ouabain to the round window membrane of the gerbil selectively induces the death of most spiral ganglion neurons and thus provides an excellent model for investigating the survival and differentiation of embryonic stem cells (ESCs) introduced into the inner ear. In this study, mouse ESCs were pretreated with a neural-induction protocol and transplanted into Rosenthal’s canal (RC), perilymph, or endolymph of Mongolian gerbils either 1–3 days (early post-injury transplant group) or 7 days or longer (late post-injury transplant group) after ouabain injury. Overall, ESC survival in RC and perilymphatic spaces was significantly greater in the early post-injury microenvironment as compared to the later post-injury condition. Viable clusters of ESCs within RC and perilymphatic spaces appeared to be associated with neovascularization in the early post-injury group. A small number of ESCs transplanted within RC stained for mature neuronal or glial cell markers. ESCs introduced into perilymph survived in several locations, but most differentiated into glia-like cells. ESCs transplanted into endolymph survived poorly if at all. These experiments demonstrate that there is an optimal time window for engraftment and survival of ESCs that occurs in the early post-injury period.
机译:哇巴因在沙鼠的圆窗膜上的应用选择性地诱导了大多数螺旋神经节神经元的死亡,从而为研究引入内耳的胚胎干细胞(ESC)的存活和分化提供了一个极好的模型。在这项研究中,小鼠胚胎干细胞经过神经诱导方案预处理,并在1-3天(损伤后早期移植组)或7天或更长时间(晚期)移植到蒙古沙鼠的卢森塔尔运河(RC),周淋巴或内淋巴中损伤后移植组)哇巴因损伤后。总体而言,在损伤后的早期微环境中,RC和淋巴管间隙中的ESC存活率明显高于损伤后的晚期。在损伤后早期组中,RC和淋巴周间隙内的可行ESC簇似乎与新生血管形成有关。少量移植到RC中的ESC对成熟的神经元或神经胶质细胞标志物染色。引入周淋巴的ESC在几个位置都可以存活,但大多数分化为胶质样细胞。移植到内淋巴中的ESC生存能力很差。这些实验表明,在损伤后的早期阶段,存在着ESC移植和存活的最佳时间窗口。

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