Experimental observation on the effect of bone marrow mesenchymal stem cells transplanting CXCR4 over gentamicin ototoxicity

Abstract

Objective: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.Method: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.Result: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(P>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(P>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(P<0.05).Fluorescence tracing showed that the number of CXCR4-BMSCs homing cells was significantly increased, and showed a cohort like arrangement.Conclusion: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.