Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects.
Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects.
复制标题
静脉注射骨髓单核细胞可通过旁分泌作用减轻短暂性耳蜗缺血后的听力损失。
DOI：
10.1097/wnr.0000000000000167
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Hakuba N.
中科院分区：
文献类型：
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作者：
Takagi T;Yoshida T;Okada M;Hata R;Hato N;Gyo K;Hakuba N.
骨髓单核细胞（BMMCs）通过分泌血管生成因子和诱导宿主组织血管生成因子的表达来促进缺血损伤后的恢复。因此，骨髓间充质干细胞移植被认为是促进缺血性损伤器官修复的潜在途径。本实验研究了骨髓间质干细胞对沙鼠短暂性耳蜗缺血后毛细胞进行性变性的影响。一过性耳蜗缺血是由于双侧椎动脉在进入颈椎横孔之前被颅外阻断而引起的。静脉注射BMMCs可预防缺血诱导的毛细胞变性并改善听力障碍。一项追踪研究显示，注入股静脉的骨髓间充质干细胞被限制在耳蜗螺旋动脉内，提示虽然移植的骨髓间充质干细胞被保留在耳蜗螺旋神经节区，但它们既没有转分化为耳蜗细胞，也没有与受损的Corti器官毛细胞和支持细胞融合以恢复其功能。我们还发现，在bmmc治疗后，Corti器官中神经营养因子-3和胶质细胞系来源的神经营养因子的蛋白水平上调。这些结果提示bmmc可能通过旁分泌作用具有治疗潜力。因此，我们建议使用bmmc作为听力损失的潜在新治疗策略。
Bone marrow mononuclear cells (BMMCs) are known to enhance recovery from ischemic insults by secreting angiogenic factors and inducing the expression of angiogenic factors from host tissues. Therefore, the transplantation of BMMCs is considered a potential approach to promoting the repair of ischemic damaged organs. Here, we investigated the influence of BMMCs on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries immediately before their entry into the transverse foramen of the cervical vertebra. An intravenous injection of BMMCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. A tracking study showed that BMMCs injected into the femoral vein were limited in the spiral artery of the cochlea, suggesting that, although transplanted BMMCs were retained within the spiral ganglion area of the cochlea, they were neither transdifferentiated into cochlear cells nor fused with the injured hair cells and supporting cells in the organ of Corti to restore their functions. We also showed that the protein level of neurotrophin-3 and glial cell line-derived neurotrophic factor in the organ of Corti was upregulated after treatment with BMMCs. These results suggested that BMMCs have therapeutic potential possibly through paracrine effects. Thus, we propose the use of BMMCs as a potential new therapeutic strategy for hearing loss.