Tan Chang-qiang, Gao Xia, Guo Lang, Huang He
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing, Jiangsu 210009, China ; Department of Otolaryngology-Head and Neck Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
Department of Otolaryngology-Head and Neck Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
Biomed Res Int. 2014;2014:856019. doi: 10.1155/2014/856019. Epub 2014 Apr 22.
Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.
表达重组白细胞介素-4的骨髓间充质干细胞（BMSCs）具有修复炎症性疾病的潜力。因此，我们研究了表达外源性白细胞介素-4的BMSCs是否能减轻自身免疫性感音神经性听力损失。从豚鼠分离的BMSCs用表达白细胞介素-4的重组慢病毒转染。总共33只动物分为三组。A组经鼓阶注射表达白细胞介素-4的BMSCs，B组经鼓阶注射表达对照载体的BMSCs，C组经鼓阶注射磷酸盐缓冲液。通过免疫组织化学和荧光显微镜评估植入的BMSCs在内耳中的分布。监测听觉脑干反应（ABR）以评估听觉变化。BMSCs移植后，A组和B组的ABR波III阈值水平降低，两组之间观察到显著差异（P<0.05）。移植的BMSCs分布在鼓阶和前庭阶。在一些听力损失的耳朵中，螺旋神经节细胞数量减少，伴有不同程度的内淋巴积水或絮状物。移植后，慢病毒感染的BMSCs迁移至内耳并产生白细胞介素-4。我们的结果表明，移植后，BMSCs和表达重组白细胞介素-4的BMSCs具有修复自身免疫性内耳疾病炎症损伤的能力。
