title: Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of autoimmune sensorineural hearing loss in a guinea pig model.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chang-qiang
authors.initials: CQ
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology, Nanjing Stomatological Hospital, Nanjing, Jiangsu 210008, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001309:Auditory Threshold; D001327:Autoimmune Diseases / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000378:metabolism*; D048430:Cell Shape; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000473:pathology / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000378:metabolism*; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D015847:Interleukin-4