title: Conditioning the cochlea to facilitate survival and integration of exogenous cells into the auditory epithelium.
abstract: The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell transplantation. Inserting stem cells into the AE of deaf ears is a complicated task due to the hostile, high potassium environment of the scala media in the cochlea, and the robust junctional complexes between cells in the AE that resist stem cell integration. Here, we evaluate whether temporarily reducing potassium levels in the scala media and disrupting the junctions in the AE make the cochlear environment more receptive and facilitate survival and integration of transplanted cells. We used sodium caprate to transiently disrupt the AE junctions, replaced endolymph with perilymph, and blocked stria vascularis pumps with furosemide. We determined that these three steps facilitated survival of HeLa cells in the scala media for at least 7 days and that some of the implanted cells formed a junctional contact with native AE cells. The data suggest that manipulation of the cochlear environment facilitates survival and integration of exogenously transplanted HeLa cells in the scala media.
authors.affiliation: 1] Department of Otolaryngology-Head and Neck Surgery, KHRI, The University of Michigan, Ann Arbor, MI, USA [2] Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, 33 Munwha Ro, Daesa Dong, Jung Gu, Daejeon, Korea [3] Brain Research Institute, College of Medicine, Chungnam National University, 33 Munwha Ro, Daesa Dong, Jung Gu, Daejeon, Korea.
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Park
authors.affiliation: Division of Otolaryngology, University of Utah, 50 North Medical Dr.3C120 SOM, Salt Lake City, UT, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Wilson
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, KHRI, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Hiu
authors.initials: H
authors.lastname: Tung Wong
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, KHRI, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Beyer
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, KHRI, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Swiderski
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, KHRI, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Dolan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, KHRI, The University of Michigan, Ann Arbor, MI, USA.
authors.forename: Yehoash
authors.initials: Y
authors.lastname: Raphael
mesh_terms: D018929:Cell Culture Techniques; D003051:Cochlea / Q000473:pathology*; D017077:Culture Media, Conditioned; D004848:Epithelium / Q000473:pathology; D006198:Hair Cells, Auditory / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D011188:Potassium / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013316:Stria Vascularis / Q000166:cytology
chemical_list: D017077:Culture Media, Conditioned; D011188:Potassium