Therapeutic Effect Of Locally Injection Of Bone-marrow Mesenchymal Stell Cells Decorated By Recombinant Vector Of Lentivirus With IL-4 Gene Into Inner Ear On Immune-mediated Immune Sensorineural Hearing Loss In Guinea Pigs

Objective: To evaluate the therapeutic effect on guinea pigs with immune-mediated sensorineural hearing loss (IMSNHL) after the local implanting with bone-marrow mesenchymal stem cells (BMMSCs) into inner ear ,which was decorated with recombinant lentivirus vocters carrying interleukin-4 (IL-4) gene.Methods: Guinea pigs were immunized with keyhole limpet hemocyanin (KLH) and caused 33 animal models, which were divided into three groups on refering to matched-pairs design. Recombinant lentiviral vector integrated IL-4 gene to infect the BMMSCs in vitro, the green fluorescence report and the result of RT-PCR to confirm the successful infection of BMMSCs. Group A and group B were implanted separately into scala tymani. Group C were injected phosphate buffer (PBS). Auditory functions and the KLH level of Guinea pigs blood were monitored respectively by ABRs and ELISA test; Fluorography immunohistochemistry test was performed for tracing BMSCs and enzyme immunohistochemistry test for the situation of IL-4 gene express and productive protein distribution in inner ear. Hematoxylin-eosin (HE) stain and light microscopy were carried out.Results: There were no significant differences in level of KLH in blood serum 2 weeks after immunization (pretransplantation) and 1 week after the transplantation of the BMMSCs in the same guinea pigs from each group. The threshold of ABRâ…¢wave decreased in group A and group B, the result was more significant in group A and group B than that in group C (P<0.05). The results of immunohistochemistry test showed that Fluorescence positive BMMSCs mainly scattered in scala tymani and scala vestibule. Enzyme immune-reaction positive product (i.e. IL-4 gene product) mainly located at spiral ganglion, Corti organ, stria vascularis, around areas of BMMSCs in cochlear duct and etc. After the transplantation of cells, the degree of immunity inflammatory reaction and level of hearing impairment were relieved. These situation was more significant in group A than that in group B.Conclusion: These results suggest that BMMSCs and BMMSCs decorated with IL-4 gene can be locally implanted into inner ear and could move forward to pathologic site, importantly develop therapeutical effect to immune-mediated sensorineural hearing loss.