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

被引：18

作者：

Takeda, Hiroki ^{[1
,2
]}

Hosoya, Makoto ^{[3
,4
]}

Fujioka, Masato ^{[3
,4
]}

Saegusa, Chika ^{[3
,4
]}

Saeki, Tsubasa ^{[3
,4
]}

Miwa, Toru ^{[1
,2
,6
,7
]}

Okano, Hideyuki ^{[5
]}

Minoda, Ryosei ^{[1
,2
,6
,7
]}

机构：

[1] Kumamoto Univ, Grad Sch Med, Dept Otolaryngol, Chuo Ku, 1-1-1 Honjo, Kumamoto, Japan

[2] Kumamoto Univ, Grad Sch Med, Dept Head & Neck Surg, Chuo Ku, 1-1-1 Honjo, Kumamoto, Japan

[3] Keio Univ, Sch Med, Dept Otolaryngol, Shinjuku Ku, 35 Shinanomachi, Tokyo, Japan

[4] Keio Univ, Sch Med, Dept Head & Neck Surg, Shinjuku Ku, 35 Shinanomachi, Tokyo, Japan

[5] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, 35 Shinanomachi, Tokyo, Japan

[6] JCHO Kumamoto Gen Hosp, Middle Ear & Inner Ear Surg Ctr, Dept Otolaryngol, 10-10 Tori Machi, Yatsushiro, Kumamoto 8668660, Japan

[7] JCHO Kumamoto Gen Hosp, Middle Ear & Inner Ear Surg Ctr, Dept Head & Neck Surg, 10-10 Tori Machi, Yatsushiro, Kumamoto 8668660, Japan

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

SENSORINEURAL HEARING-LOSS; RESCUES HEARING; MOUSE MODEL; IN-VITRO; CONNEXIN26; DELETION; GENE; IMPAIRMENT; MUTATIONS; PHENOTYPE;

D O I：

10.1038/s41598-018-20277-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 35 条

[1] Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness [J].