Regeneration of the cochlear cells by bone marrow stem cells

本研究的目的是评价造血干细胞(HSCs)或由其分化而来的免疫活性细胞在老年性感音神经性耳聋(SNHL)耳蜗细胞再生或退化中的作用。将BALB/c、C57BL/6和绿色荧光蛋白C57BL/6转基因小鼠作为慢性老年性耳聋的正常小鼠，将包括HSC在内的骨髓细胞按常规骨髓移植的方法静脉接种，或植入骨髓腔内，以维持与移植前相似的宿主免疫功能。结果表明，两种动物模型的SNHL和耳蜗变性都不是由于耳蜗骨的缺陷造成的，而是由于转移计划…导致的HSC和来源于HSC的免疫活性细胞的缺陷所致多移植正常小鼠的骨髓可预防或恢复MRL/LPR小鼠血管纹或SAMP1小鼠螺旋神经节(SG)细胞变性的SNHL，这也是因为移植有耳蜗病的SNHL模型小鼠的骨髓可导致与正常小鼠相同的听力损失和病理改变。当免疫功能受损时，这些小鼠表现出SNHL的侵袭性发展和SG的变性。这些结果表明，不仅基因背景和免疫功能影响SAMP1小鼠的神经发生系统。免疫荧光研究表明，移植GEP小鼠骨髓细胞的SNHL小鼠的耳蜗内没有观察到包括HSCs和免疫活性细胞在内的供体细胞，从而防止了SNHL和耳蜗组织的退化。此外，MRL/LPR和SAMP1小鼠均表现出与年龄相关的Th细胞功能障碍。综上所述，耳蜗细胞不是由局部浸润性细胞(包括HSCs和免疫活性细胞)再生或维持的，而是由体液因子通过血-内耳屏障进行管理的，如全身Th细胞释放的细胞因子，这可能在SNHL的慢性发展治疗中发挥关键作用。较少

The aim of the current study was to evaluate function of hemopoietic stem cells (HSCs) or immunocompetent cells differentiated from those stem cells in regeneration or degeneration of the cochlear cells associated with age-related sensorineural hearing loss (SNHL).As animal models of accelerated age-related SNHL, two murine substrains, the MRL/lpr mouse and SAMP1 mouse were used. As normal mice which show slow presbycusis, BALB/c, C57BL/6, or GFP (green fluorescence protein) mice which is C57BL/6 transgenic mice with GFP DNA were used.Bone marrow cells including HSCs were inoculated intravenously as conventional bone marrow transplantation (BMT), or into bone marrow cavity (intra-BMT) which can maintain the host immune function similar to the function of pre-transplantation.The results indicated that SNHL and cochlear degeneration in both animal models do not result from defects in the cochlea but do from defects in HSCs and immunocompetent cells derived from the HSCs because transplan … More tation of bone marrow from normal mice prevented or recovered the SNHL with degeneration of the stria vascularis in MRL/lpr mice, or of the spiral ganglion (SG) cells in SAMP1 mice, and also because transplantation of bone marrow from the murine models of SNHL with cochlear pathology caused the same hearing loss and pathology in the normal mice.The relationship between presbycusis and the immune system was also analyzed using SAMP1 mice. When the immune functions were impaired, these mice showed aggressive development of SNHL and degeneration of the SG. These findings indicate that not only the gene backgrounds but also immune functions affect the neurogeneration system in SAMP1 mice.Immunofluorescence study indicated that donor cells including HSCs and immunocompetent cells were not observed in the cochlea of the SNHL mice which had been transplanted bone marrow cells from the GEP mice and prevented SNHL and degeneration of the cochlea. In addition, both MRL/lpr and SAMP1 mice showed age-related dysfunctions of Th cells. These findings taken together indicate that cochlear cells are not regenerated or maintained by local infiltrated cells including HSCs and immunocompetent cells but are managed by humoral factors, through the blood-inner ear barrier, such as cytokines released by systemic Th cells, which may play key role of therapy for chronic development of SNHL. Less