title: The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.
abstract: The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally.
authors.affiliation: StemGen Therapeutics, LLC, Austin, TX, USA; StemGen Korea Inc, Seoul, South Korea; University of Tennessee HSC, Memphis, TN, USA. Electronic address: taijuneyoo@gmail.com.
authors.forename: T J
authors.initials: TJ
authors.lastname: Yoo
authors.affiliation: Hough Ear Institute, Oklahoma City, OK, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Du
authors.affiliation: University of Tennessee HSC, Memphis, TN, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D003051:Cochlea / Q000503:physiopathology; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006309:Hearing; D006319:Hearing Loss, Sensorineural / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009925:Organ of Corti / Q000378:metabolism / Q000503:physiopathology; D019899:Paracrine Communication; D013136:Spiral Ganglion / Q000378:metabolism / Q000503:physiopathology; D055493:Spiral Ligament of Cochlea / Q000378:metabolism; D013316:Stria Vascularis / Q000378:metabolism; D014404:Tubulin / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D014404:Tubulin
keywords: Autoimmune hearing loss; Paracrine activity; Stem cell therapy