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Sci Rep. 2018 Jan 31;8(1):1941. doi: 10.1038/s41598-018-20277-5.

Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.

Author information

1
Departments of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto city, Japan.
2
Departments of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
3
Departments of Otolaryngology-Head and Neck Surgery, Middle Ear and Inner Ear Surgical Center, JCHO Kumamoto General Hospital, 10-10 Tori Machi, Yatsushiro, Kumamoto, 866-8660, Japan.
4
Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, Japan.
5
Departments of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine, 1-1-1 Honjo, Chuoku, Kumamoto city, Japan. ryminoda@gmail.com.
6
Departments of Otolaryngology-Head and Neck Surgery, Middle Ear and Inner Ear Surgical Center, JCHO Kumamoto General Hospital, 10-10 Tori Machi, Yatsushiro, Kumamoto, 866-8660, Japan. ryminoda@gmail.com.

Abstract

There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

PMID:
29386634
PMCID:
PMC5792596
DOI:
10.1038/s41598-018-20277-5
[Indexed for MEDLINE]
Free PMC Article

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