Engraftment of Human Stem Cell-Derived Otic Progenitors in the Damaged Cochlea.
Amikacin
/ adverse effects
Animals
Auditory Threshold
/ drug effects
Cell Differentiation
/ drug effects
Cell Enlargement
Cell Movement
/ drug effects
Cyclosporine
/ pharmacology
Disease Models, Animal
Fibroblast Growth Factor 10
/ pharmacology
Fibroblast Growth Factor 3
/ pharmacology
Guinea Pigs
Hair Cells, Auditory
/ drug effects
Hearing Loss
/ chemically induced
Humans
Immunosuppressive Agents
/ pharmacology
Induced Pluripotent Stem Cells
/ immunology
Living Donors
Ototoxicity
/ surgery
Stem Cell Transplantation
/ methods
animal model of ototoxicity
cell injection assay
engraftment
human induced pluripotent cells
in vitro otic model
migration
otic progenitor cells
sensory cell differentiation
transplantation
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
05 06 2019
05 06 2019
Historique:
received:
18
10
2018
revised:
25
03
2019
accepted:
26
03
2019
pubmed:
22
4
2019
medline:
9
4
2020
entrez:
22
4
2019
Statut:
ppublish
Résumé
Most cases of sensorineural deafness are caused by degeneration of hair cells. Although stem/progenitor cell therapy is becoming a promising treatment strategy in a variety of organ systems, cell engraftment in the adult mammalian cochlea has not yet been demonstrated. In this study, we generated human otic progenitor cells (hOPCs) from induced pluripotent stem cells (iPSCs) in vitro and identified these cells by the expression of known otic markers. We showed successful cell transplantation of iPSC-derived-hOPCs in an in vivo adult guinea pig model of ototoxicity. The delivered hOPCs migrated throughout the cochlea, engrafted in non-sensory regions, and survived up to 4 weeks post-transplantation. Some of the engrafted hOPCs responded to environmental cues within the cochlear sensory epithelium and displayed molecular features of early sensory differentiation. We confirmed these results with hair cell progenitors derived from Atoh1-GFP mice as donor cells. These mouse otic progenitors transplanted using the same in vivo delivery system migrated into damaged cochlear sensory epithelium and adopted a partial sensory cell fate. This is the first report of the survival and differentiation of hOPCs in ototoxic-injured mature cochlear epithelium, and it should stimulate further research into cell-based therapies for treatment of deafness.
Identifiants
pubmed: 31005598
pii: S1525-0016(19)30112-1
doi: 10.1016/j.ymthe.2019.03.018
pmc: PMC6554666
pii:
doi:
Substances chimiques
Fibroblast Growth Factor 10
0
Fibroblast Growth Factor 3
0
Immunosuppressive Agents
0
Cyclosporine
83HN0GTJ6D
Amikacin
84319SGC3C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1101-1113Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC014089
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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