Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea.
Medical Laser Research Center, Dankook University, Cheonan 31116, Republic of Korea.
Biomed Res Int. 2021 Jun 21;2021:4956404. doi: 10.1155/2021/4956404. eCollection 2021.
Hearing loss is a sensory deprivation that can affect the quality of life. Currently, only rehabilitation devices such as hearing aids and cochlear implants are used, without a definitive cure. However, in chronic hearing-deprived patients, in whom secondary auditory neural degeneration is expected, a relatively poor rehabilitation prognosis is projected. Stem cell therapy for cochlear neural structures would be an easier and feasible strategy compared with cochlear sensory cells. Considering the highly developed cochlear implantation technology, improving cochlear neural health has significant medical and social effects. Stem cell delivery to Rosenthal's canal in an acutely damaged mouse model has been performed and showed cell survival and the possibility of differentiation. The results of stem cell transplantation in chronic auditory neural hearing loss should be evaluated because neural stem cell replacement therapy for chronic (long-term) sensorineural hearing loss is a major target in clinics. In the present study, we established a mouse model that mimicked chronic auditory neural hearing loss (secondary degeneration of auditory neurons after loss of sensory input). Then, mouse embryonic stem cells (mESCs) were transplanted into the scala tympani and survival and distribution of transplanted cells were compared between the acute and chronic auditory neural hearing loss models induced by ouabain or kanamycin (KM), respectively. The mESC survival was similar to the acute model, and perilymphatic distribution of cell aggregates was more predominant in the chronic model. Lastly, the effects of mESC transplantation on neural signal transduction observed in the cochlear nucleus (CN) were compared and a statistical increase was observed in the chronic model compared with other models. These results indicated that after transplantation, mESCs survived in the cochlea and increased the neural signaling toward the central auditory pathway, even in the chronic (secondary) hearing loss mouse model.
听力损失是一种感觉剥夺，会影响生活质量。目前，仅使用助听器和人工耳蜗等康复设备，尚无明确的治愈方法。然而，在预期会发生继发性听觉神经退行性变的慢性听力丧失患者中，预计康复预后较差。与耳蜗感觉细胞相比，耳蜗神经结构的干细胞治疗将是一种更容易和可行的策略。考虑到高度发达的耳蜗植入技术，改善耳蜗神经健康具有重要的医学和社会影响。已经在急性损伤的小鼠模型中进行了向 Rosenthal 管输送干细胞的实验，结果显示细胞存活和分化的可能性。应该评估慢性听觉神经听力损失中干细胞移植的结果，因为慢性（长期）感觉神经性听力损失的神经干细胞替代治疗是临床的主要目标。在本研究中，我们建立了一种模拟慢性听觉神经听力损失的小鼠模型（感觉输入丧失后听觉神经元的继发性退化）。然后，将小鼠胚胎干细胞（mESC）移植到鼓阶，比较分别用哇巴因或卡那霉素（KM）诱导的急性和慢性听觉神经听力损失模型中移植细胞的存活和分布。mESC 的存活与急性模型相似，而在慢性模型中，细胞聚集体的外淋巴分布更为明显。最后，比较了 mESC 移植对耳蜗核（CN）中神经信号转导的影响，与其他模型相比，慢性模型中的神经信号转导呈统计学增加。这些结果表明，移植后 mESC 在耳蜗中存活，并增加了向中枢听觉通路的神经信号，即使在慢性（继发性）听力丧失小鼠模型中也是如此。
