Regeneration of the cochlear cells by bone marrow stem cells

为探讨造血干细胞（hemopoietic stem cells，HSCs）及其分化的免疫活性细胞在增龄性感音神经性聋（senorineural hearing loss，SNHL）耳蜗细胞再生或变性中的作用，本研究采用MRL/lpr小鼠和SAMP 1小鼠作为加速增龄性SNHL的动物模型。BALB/c、C57 BL/6、GFP小鼠与正常小鼠一样，使用具有GFP DNA的C57 BL/6转基因小鼠（绿色荧光蛋白）小鼠，静脉内接种包括HSC的骨髓细胞作为常规骨髓移植（BMT），或进入骨髓腔（内BMT），它可以维持宿主免疫功能类似的功能，结果表明，在两种动物模型中，SNHL和耳蜗变性不是由于耳蜗缺陷，而是由于HSC和来自HSC的免疫活性细胞的缺陷，因为移植物的存在是导致SNHL和耳蜗变性的主要原因。 ...更多信息 正常小鼠骨髓移植预防或恢复了SNHL，MRL/lpr小鼠血管纹变性，或SAMP 1小鼠螺旋神经节（SG）细胞变性，同时，由于移植SNHL模型鼠骨髓后，其耳蜗病理改变与正常鼠相同，故本研究还采用SAMP 1. 0分析了老年性聋与免疫系统的关系小鼠当免疫功能受损时，这些小鼠表现出SNHL的侵袭性发展和SG的变性。免疫荧光研究表明，移植GEP小鼠骨髓细胞后的SNHL小鼠耳蜗内未观察到包括HSC和免疫活性细胞在内的供体细胞，其对SNHL和耳蜗退变有一定的预防作用。此外，MRL/lpr和SAMP 1小鼠均表现出与年龄相关的Th细胞功能障碍。这些发现表明耳蜗细胞不是由局部浸润的细胞（包括HSC和免疫活性细胞）再生或维持的，而是由体液因素通过血液-内耳屏障管理的，例如系统性Th细胞释放的细胞因子，这可能在SNHL慢性发展的治疗中起关键作用。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