Huang S P, Wang X Y, Fang C, Wang X Y, Wu Q
Department of Otorhinolaryngology, Provincial Clinical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, China.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Mar;32(5):355-359. doi: 10.13201/j.issn.1001-1781.2018.05.009.
To observe the survival and migration ability of CXCR4-BMSCs in guinea pig cochlea with gentamycin induced sensorineural hearing loss, and to explore whether SDF-1/CXCR4 axis can mediate bone marrow mesenchymal stem cells (BMSCs) to cochlear homing.BMSCs were isolated and extracted from guinea pigs. A bone marrow mesenchymal stem cell line with overexpression of CXCR4 was established. The animal model of sensorineural deafness was established by intraperitoneal injection of gentamicin［100 mg/(kg·d)］in 50 healthy guinea pigs. The successful deafness animals were randomly divided into three groups(14 rats in each group): sterilizing water group, BMSCs transplantation group and CXCR4-BMSCs transplantation group.Auditory brainstem response(ABR) were performed at 2 weeks and 4 weeks respectively after the tansplantation through cochlear tympanic pathway. The directional homing of the implanted cells in the cochlea was traced by the frozen section fluorescence of the cochlear tissue.The hearing thresholds of the three groups were (91.3±5.2),(90.7±4.8)and (90.9±5.6)dB (SPL) respectively. There was no significant difference among them(>0.05). In sterile Water group, the hearing thresholds were(89.7±6.4)dB and (89.2±6.7)dB respectively when detected on 2 and 4 weeks after transplantation. There were no significant difference(>0.05);In BMSCs group, the hearing thresholds were (88.6±5.3)dB(SPL) on 2 weeks and (78.4±7.3)dB(SPL) on 4 weeks after transplantation. In CXCR4-BMSCs group, the hearing thresholds were(75.3±7.8)dB(SPL) on 2 weeks and (62.1±8.4)dB(SPL) on 4 weeks after transplantation. The differences were statistically significant (PThe hearing threshold was (75.3±7.8)dB (SPL) at 2 weeks after operation. The hearing enhancement was about 15 dB, the hearing threshold was (62.1±8.4)dB(SPL) at 4 weeks, the difference was statistically significant(<0.05).Fluorescence tracing showed that the number of CXCR4-BMSCs homing cells was significantly increased, and showed a cohort like arrangement.The SDF-1/CXCR4 axis plays an important role in the directional homing and differentiation of the cells into the cochlea, which can improve the hearing repair ability of guinea pigs induced by gentamicin induced sensorineural deafness.
观察CXCR4基因修饰的骨髓间充质干细胞（CXCR4-BMSCs）在庆大霉素致豚鼠感音神经性聋模型耳蜗内的存活及迁移能力，探讨基质细胞衍生因子-1（SDF-1）/CXCR4轴能否介导骨髓间充质干细胞（BMSCs）向耳蜗归巢。从豚鼠体内分离提取BMSCs，构建CXCR4基因过表达的骨髓间充质干细胞系。将50只健康豚鼠腹腔注射庆大霉素［100 mg/(kg·d)］建立感音神经性聋动物模型。将造模成功的动物随机分为3组（每组14只）：生理盐水组、BMSCs移植组和CXCR4-BMSCs移植组。分别于移植后2周、4周经耳蜗鼓阶途径进行听性脑干反应（ABR）检测。通过耳蜗组织冰冻切片荧光法追踪植入细胞在耳蜗内的定向归巢情况。3组术后即刻听阈分别为（91.3±5.2）、（90.7±4.8）和（90.9±5.6）dB（SPL），组间差异无统计学意义（>0.05）。生理盐水组术后2周、4周听阈分别为（89.7±6.4）dB和（89.2±6.7）dB，差异无统计学意义（>0.05）；BMSCs移植组术后2周听阈为（88.6±5.3）dB（SPL），4周为（78.4±7.3）dB（SPL）；CXCR4-BMSCs移植组术后2周听阈为（75.3±7.8）dB（SPL），4周为（62.1±8.4）dB（SPL），差异有统计学意义（P<0.05）。CXCR4-BMSCs移植组术后2周听阈为（75.3±7.8）dB（SPL），听力提高约15 dB，4周时听阈为（62.1±8.4）dB（SPL），差异有统计学意义（<0.05）。荧光示踪显示，CXCR4-BMSCs归巢细胞数量明显增多，呈队列样排列。SDF-1/CXCR4轴在细胞向耳蜗定向归巢及分化过程中起重要作用，可提高庆大霉素致豚鼠感音神经性聋后的听力修复能力。
