title: Transplanting mouse induced pluripotent stem cells into mouse otocysts in vivo.
abstract: The otocyst is an attractive target for studying treatment strategies for genetic hearing loss and for understanding inner ear development. We have previously reported that trans-uterine supplemental gene therapy in vivo into the otocysts of mice, which had a loss of function mutation in a causative gene of deafness, was able to prevent putative hearing loss. We herein set out to clarify the feasibility of allogenic cell transplantation into the mouse otocysts in vivo. We transplanted naive mouse-derived induced pluripotent stem cells (miPSCs) into the otocysts of wild type mice or connexin (Cx) 30 deficient mice, at embryonic day 11.5 (E11.5). The transplanted m-iPSCs survived in the lumens of the inner ears at E13.5 and E15.5 in wild type mice. In the Cx30 deficient mouse, the transplanted cells survived similarly, with some of the transplanted cells migrating into the lining cells of the lumens of the inner ears at E13.5 and showing tumorigenic cell proliferation at E15.5. In addition, engrafted cells appear to be able to differentiate after the cell transplantation. Our results suggest that otocyst transplanted cells survived and differentiated. A Cx30 deficiency may facilitate cell migration. These findings may offer some hope for cell transplantation therapy for profound genetic hearing loss caused by a Cxs deficiency.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto City 860-0811, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto City 860-0811, Japan. Electronic address: minoda@gpo.kumamoto-u.ac.jp.
authors.forename: Ryosei
authors.initials: R
authors.lastname: Minoda
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto City 860-0811, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Miwa
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto City 860-0811, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kumamoto University, Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto City 860-0811, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Ise
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics; D007758:Ear, Inner / Q000166:cytology* / Q000196:embryology; D004847:Epithelial Cells / Q000166:cytology; D005240:Feasibility Studies; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D018345:Mice, Knockout
chemical_list: D000075302:Connexin 30; D017630:Connexins; C100629:Gjb6 protein, mouse
keywords: Cell transplantation; Connexin 30; Otocyst; Tumorigenesis; iPS