Gene Therapy of Inner Ear Injection with Bone -Marrow Mesenchymal Stem Cells Decorated with Interleukin-4 Gene on Immune-Mediated Inner Ear Disease in Guinea Pigs / 听力学及言语疾病杂志

ABSTRACT

Objective To evaluate the gene therapeutic effects of guinea pigs model with immune -mediated inner ear disease(IMIED)after locally injection of bone -marrow mesenchymal stem cells(BMSCs) decorated by in-terleukin-4 gene .Methods Guinea pigs were immunized with keyhole limpet hemocyanin (KLH) and caused 55 animal models ,divided into five groups ,each group with 11 animals :groupA(BMSCs carrier) ,group B(BMSCs emp-ty -carrier control group) ,group C(recombinent lentivirus IL -4 gene) ,group D(lentivirus empty -carrier control group) ,group E(simulation operation control group) .Groups were all injected with the corresponding suspension (20 μl)[includs BMSCs ceas of (1 .5~2 .0) × 106 ,the concentration of (entivirus) is 0 .5 × 108 pfu] by the scala tympani window into the inner ear .The fluorography immunohistochemistry test and enzyme immunohistochemistry test for the situation of IL -4 gene express and productive protein distribution in inner ear .Auditory functions and the KLH level of guinea pigs blood were monitored respectively by auditory brainstem responses (ABRs) and ELISA test .Results The threshold of ABR wave Ⅲ decreased in group A ,group B and group C .The result were more significant in group A and group B than that in group C ,but results in group A was more prominent (P<0 .05) . The results of immunohistochemistry test showed that fluorescence positive BMSCs mainly scattered in scala tymani and scala vestibule .The microscope results showed that for the group A ,B and C ,there were only few foccule and red and white blood cells in scala tympani floc ,but for group D and group E ,with different levels of labyrinthine hy-drops and some mononuclear cells around the spiral ganglion and small blood vessels .Conclusion Restructuring lentiviral vector with IL -4 gene can be successfully transfected into BMSCs in vitro ,compared to inplangting into inner ear in scala tympani approach ,the cells can migrate and generate gene product of IL -4 ,to significantly im-prove the auditory functions and inflammatory reaction of inner ear disease ,and BMSCs can be used as a carrier to migrate to the damaged part with therapeutic gene .