Transplantation of mouse-induced pluripotent stem cells into the cochlea for the treatment of sensorineural hearing loss

Abstract

Conclusion: Mouse-induced pluripotent stem cells (iPSCs) could differentiate into hair cell-like cells and spiral ganglion-like cells after transplantation into mouse cochleae, but it cannot improve the auditory brain response (ABR) thresholds in short term.

Objective: To evaluate the potential of iPSCs for use as a source of transplants for the treatment of sensorineural hearing loss (SNHL).

Methods: Establishing SNHL mice model, then injecting the iPSCs or equal volume DMEM basic medium into the cochleae, respectively. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) were used to assess the survival, migration, differentiation of the transplanted iPSCs in cochleae and then recorded the ABR threshold in different time. Hematoxylin–eosin (HE) staining was used to observe the teratoma formation.

Results: Four weeks after transplantation, CM-Di1-labeled iPSCs could be found in the modiolus and Rosenthal’s canal (RC), and some of them could expressed auditory hair cell markers or spiral ganglion neuron makers in group A, but not found in group B and C. As to the ABR threshold, no significance differences were found between pre- with postoperative in group A or B. In our study, no teratoma was observed in the cochleae.

Chinese abstract

结论：小鼠诱导的多能干细胞（iPSCs）在移植到小鼠耳蜗后可分化为毛细胞样细胞和螺旋神经节样细胞, 但它在短期内不能改善听觉脑反应（ABR）阈值。

目的：评估iPSCs作为移植手段治疗感觉神经性听力损失（SNHL）的潜力。

方法：建立SNHL小鼠模型, 然后分别将iPSC或等体积的DMEM基础培养基注入耳蜗。免疫荧光染色和逆转录聚合酶链反应（RT-PCR）用于评估移植的iPSCs在耳蜗中的存活、迁移和分化, 然后记录不同时间的ABR阈值。使用苏木精 - 伊红（HE）染色观察畸形瘤的形成。

结果：移植后4周, CM-Di1标记的iPSC可以在组织和Rosenthal耳道（RC）中发现, 其中一些可以在A组中表现为听觉毛细胞标志物或螺旋神经节神经元制造者, 但在B和C组中没有发现。.对于ABR阈值, A组或B组在术前术后未发现显著性差异。在我们的研究中, 耳蜗中没有观察到畸形瘤。

Keywords:

• Induced pluripotent stem cells
• inner ear transplantation
• auditory hair cells
• spiral ganglion
• cell differentiation
• cell therapy

Acknowledgments

This study was supported by the National Natural Science Grants of China (No.81160126). We thank Hong Tu for his advise of statistical analysis, and Yanhong Chen for her advise of anatomy of cochlea.

Disclosures statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This study was supported by the National Natural Science Grants of China (No.81160126).