Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects
Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects
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DOI：
10.1016/j.neuroscience.2006.12.067
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发表时间：
2007-03
期刊：
影响因子：
3.3
通讯作者：
Tadashi Yoshida;N. Hakuba;Isao Morizane;Kensuke Fujita;Fang Cao;Pengxiang Zhu;N. Uchida;Kenji Kameda;M. Sakanaka;K. Gyo;Ryuji Hata
中科院分区：
文献类型：
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作者：
Tadashi Yoshida;N. Hakuba;Isao Morizane;Kensuke Fujita;Fang Cao;Pengxiang Zhu;N. Uchida;Kenji Kameda;M. Sakanaka;K. Gyo;Ryuji Hata
造血干细胞移植被认为是促进受损器官修复的潜在途径。在这里，我们研究了造血干细胞对沙土鼠耳蜗短暂缺血后进行性毛细胞变性的影响。在双侧椎动脉进入颈椎横突孔之前，通过颅外阻塞双侧椎动脉来产生短暂的耳蜗缺血。胼胝体内注射HSC可预防缺血诱导的毛细胞变性，并改善听力损伤。我们还发现，胶质细胞源性神经营养因子（GDNF）的蛋白水平在Corti器官上调后耳蜗缺血和HSC治疗增强缺血诱导的GDNF上调。一项追踪研究显示，注射到耳蜗中的HSC保留在耳蜗的外淋巴间隙中，尽管它们既没有转分化成耳蜗细胞类型，也没有在缺血后与受损的毛细胞融合，这表明HSC可能通过旁分泌效应具有治疗潜力。因此，我们建议HSC作为一种潜在的新的听力损失治疗策略。
Transplantation of hematopoietic stem cells (HSCs) is regarded to be a potential approach for promoting repair of damaged organs. Here, we investigated the influence of hematopoietic stem cells on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries just before their entry into the transverse foramen of the cervical vertebra. Intrascalar injection of HSCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. We also showed that the protein level of glial cell line-derived neurotrophic factor (GDNF) in the organ of Corti was upregulated after cochlear ischemia and that treatment with HSCs augmented this ischemia-induced upregulation of GDNF. A tracking study revealed that HSCs injected into the cochlea were retained in the perilymphatic space of the cochlea, although they neither transdifferentiated into cochlear cell types nor fused with the injured hair cells after ischemia, suggesting that HSCs had therapeutic potential possibly through paracrine effects. Thus, we propose HSCs as a potential new therapeutic strategy for hearing loss.