title: Survival of human embryonic stem cells implanted in the guinea pig auditory epithelium.
abstract: Hair cells in the mature cochlea cannot spontaneously regenerate. One potential approach for restoring hair cells is stem cell therapy. However, when cells are transplanted into scala media (SM) of the cochlea, they promptly die due to the high potassium concentration. We previously described a method for conditioning the SM to make it more hospitable to implanted cells and showed that HeLa cells could survive for up to a week using this method. Here, we evaluated the survival of human embryonic stem cells (hESC) constitutively expressing GFP (H9 Cre-LoxP) in deaf guinea pig cochleae that were pre-conditioned to reduce potassium levels. GFP-positive cells could be detected in the cochlea for at least 7 days after the injection. The cells appeared spherical or irregularly shaped, and some were aggregated. Flushing SM with sodium caprate prior to transplantation resulted in a lower proportion of stem cells expressing the pluripotency marker Oct3/4 and increased cell survival. The data demonstrate that conditioning procedures aimed at transiently reducing the concentration of potassium in the SM facilitate survival of hESCs for at least one week. During this time window, additional procedures can be applied to initiate the differentiation of the implanted hESCs into new hair cells.
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.|Department of Otorhinolaryngology and Head &Neck Surgery, Dankook University Hospital, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam, 31116, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hackelberg
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Kari L
authors.initials: KL
authors.lastname: Green
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Lunghamer
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kurioka
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Loomis
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Swiderski
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Duncan
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.
authors.forename: Yehoash
authors.initials: Y
authors.lastname: Raphael
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002208:Caproates / Q000494:pharmacology; D002452:Cell Count; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003053:Cochlear Duct / Q000187:drug effects; D003638:Deafness / Q000503:physiopathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000166:cytology*; D006367:HeLa Cells; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D009925:Organ of Corti / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D033581:Stem Cell Transplantation
chemical_list: D002208:Caproates; D049452:Green Fluorescent Proteins; C037652:hexanoic acid