Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.
Hiroki TakedaMakoto HosoyaMasato FujiokaChika SaegusaTsubasa SaekiToru MiwaHideyuki OkanoRyosei MinodaPublished in: Scientific reports (2018)
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.
Keyphrases
- wild type
- induced pluripotent stem cells
- induced apoptosis
- cell therapy
- high fat diet induced
- hearing loss
- cell cycle arrest
- single cell
- endothelial cells
- genome wide
- pregnant women
- stem cells
- cell death
- randomized controlled trial
- oxidative stress
- clinical trial
- copy number
- gene expression
- dna methylation
- type diabetes
- adipose tissue
- bone marrow
- combination therapy
- rectal cancer
- study protocol
- hematopoietic stem cell
- smoking cessation