Chang So-Young, Kim Eunjeong, Carpena Nathaniel T, Lee Jae-Hun, Kim Doo Hee, Lee Min Young
Beckman Laser Institute Korea, Dankook University, Cheonan 31116, Republic of Korea.
Department of Biological Science, College of Science & Technology, Dankook University, Cheonan 31116, Republic of Korea.
Stem Cells Int. 2023 Nov 15;2023:6845571. doi: 10.1155/2023/6845571. eCollection 2023.
Sensorineural hearing loss is very difficult to treat. Currently, one of the techniques used for hearing rehabilitation is a cochlear implant that can transform sound into electrical signals instead of inner ear hair cells. However, the prognosis remains very poor if sufficient auditory nerve cells are not secured. In this study, the effect of mouse embryonic stem cells (mESC) and photobiomodulation (PBM) combined treatment on auditory function and auditory nerve cells in a secondary neuropathy animal model was investigated. To confirm the engraftment of stem cells in vitro, cochlear explants were treated with kanamycin (KM) to mimic nerve damage and then cocultured with GFP-mESC. GFP-mESCs were observed to have attached and integrated into the explanted samples. An animal model for secondary neurodegeneration was achieved by KM treatment and was treated by a combination therapy of GFP-mESC and NIR-PBM at 8 weeks of KM treatment. Hearing recovery by functional testing using auditory brain stem response (ABR) and eABR was measured as well as morphological changes and epifluorescence analysis were conducted after 2 weeks of combination therapy. KM treatment elevated the hearing threshold at 70-80 dB and even after the combination treatment with GFP-mESC and PBM was applied, the auditory function was not restored. In addition, the stem cells transplanted into cochlea has exponentially increased due to PBM treatment although did not produce any malignancy. This study confirmed that the combined treatment with mESC and PBM could not improve hearing or increase the response of the auditory nerve. Nevertheless, it is noteworthy in this study that the cells are distributed in most cochlear tissues and the proliferation of stem cells was very active in animals irradiated with PBM compared to other groups wherein the stem cells had disappeared immediately after transplantation or existed for only a short period of time.
感音神经性听力损失很难治疗。目前,用于听力康复的技术之一是人工耳蜗,它可以将声音转化为电信号,而不是通过内耳毛细胞。然而,如果没有足够的听觉神经细胞,预后仍然非常差。在本研究中,研究了小鼠胚胎干细胞(mESC)和光生物调节(PBM)联合治疗对继发性神经病变动物模型的听觉功能和听觉神经细胞的影响。为了在体外确认干细胞的植入,用卡那霉素(KM)处理耳蜗外植体以模拟神经损伤,然后与绿色荧光蛋白标记的小鼠胚胎干细胞(GFP-mESC)共培养。观察到GFP-mESC附着并整合到外植体样本中。通过KM处理建立继发性神经退行性变动物模型,并在KM处理8周后用GFP-mESC和近红外光生物调节(NIR-PBM)联合治疗。在联合治疗2周后,通过听觉脑干反应(ABR)和扩展ABR(eABR)功能测试测量听力恢复情况,并进行形态学变化和落射荧光分析。KM处理使听力阈值提高到70-80分贝,即使应用GFP-mESC和PBM联合治疗后,听觉功能也未恢复。此外,尽管没有产生任何恶性肿瘤,但由于PBM处理,移植到耳蜗中的干细胞呈指数增加。本研究证实,mESC和PBM联合治疗不能改善听力或增加听觉神经的反应。然而,本研究值得注意的是,与其他组相比,干细胞在大多数耳蜗组织中分布,并且在接受PBM照射的动物中干细胞增殖非常活跃,在其他组中干细胞移植后立即消失或仅存在很短时间。