Background

The aim of this study was to investigate the potential of using bone marrow mesenchymal stem cells (BMSCs) for treatment of inflammation and autoimmune sensorineural hearing loss.

Methods

Fifty-five immunized guinea pigs were divided into five groups. Group A received BMSCs expressing IL-4, group B received BMSCs expressing an empty carrier vector, group C received recombinant lentivirus expressing IL-4, group D received recombinant lentivirus expressing an empty carrier vector, and group E received phosphate-buffered saline. Auditory function was monitored using brain stem responses (ABRs) to evaluate the auditory changes. The distribution of implanted BMSCs in the inner ear was estimated using fluorescence microscopy. The distribution and expression of IL-4 gene products in the inner ear were detected via immunohistochemistry.

Results

After transplantation, the ABR III wave threshold decreased significantly in BMSCs expressing exogenous IL-4 group (group A), BMSCs expressing empty carrier vector group (group B), and recombinant lentivirus expressing IL-4 group (group C) (P < 0.001), which means the auditory functions of the experimental guinea pigs were improved. Further statistical analysis revealed that BMSCs expressing exogenous IL-4 group (group A) and BMSCs expressing empty carrier vector group (group B) were able to improve the auditory function more obviously (P < 0.05). Lentivirus-infected BMSCs were able to migrate to the inner ear. Fluorescence-positive BMSCs were scattered in the scala tympani and vestibule.

Conclusions

These results demonstrated that BMSCs expressing exogenous IL-4 successfully migrated into the inner ear in an in vitro study. BMSCs expressing exogenous IL-4 and BMSCs can be used to treat inflammatory injury in autoimmune inner ear diseases.

中文翻译：

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基因修饰骨髓间充质干细胞在耳蜗细胞治疗中的应用

背景

本研究的目的是研究使用骨髓间充质干细胞 (BMSCs) 治疗炎症和自身免疫性感觉神经性听力损失的潜力。

方法

五十五只免疫豚鼠被分成五组。A组接受表达IL-4的BMSCs，B组接受表达空载体的BMSCs，C组接受表达IL-4的重组慢病毒，D组接受表达空载体的重组慢病毒，E组接受磷酸盐缓冲液。使用脑干反应 (ABR) 监测听觉功能以评估听觉变化。使用荧光显微镜估计植入的 BMSCs 在内耳中的分布。免疫组化检测IL-4基因产物在内耳中的分布和表达。

结果

移植后，表达外源IL-4的BMSCs组（A组）、表达空载体的BMSCs组（B组）和表达IL-4的重组慢病毒组（C组）的ABR III波阈值显着降低（P  < 0.001 )，这意味着实验豚鼠的听觉功能得到了改善。进一步统计分析发现，表达外源IL-4的BMSCs组（A组）和表达空载体载体的BMSCs组（B组）能够更明显地改善听觉功能（P  < 0.05）。慢病毒感染的骨髓间充质干细胞能够迁移到内耳。荧光阳性骨髓间充质干细胞散在鼓阶和前庭。

结论

这些结果表明，在体外研究中，表达外源性 IL-4 的 BMSCs 成功迁移到内耳。表达外源性 IL-4 的 BMSCs 和 BMSCs 可用于治疗自身免疫性内耳疾病的炎症损伤。