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Mol Ther ; 27(6): 1101-1113, 2019 06 05.
Article in English | MEDLINE | ID: mdl-31005598

ABSTRACT

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.


Subject(s)
Cell Enlargement , Hair Cells, Auditory/drug effects , Hearing Loss/surgery , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/transplantation , Ototoxicity/surgery , Stem Cell Transplantation/methods , Amikacin/adverse effects , Amikacin/pharmacology , Animals , Auditory Threshold/drug effects , Cell Differentiation/drug effects , Cell Movement/drug effects , Cyclosporine/pharmacology , Disease Models, Animal , Fibroblast Growth Factor 10/pharmacology , Fibroblast Growth Factor 3/pharmacology , Guinea Pigs , Hair Cells, Auditory/immunology , Hair Cells, Auditory/metabolism , Hearing Loss/chemically induced , Humans , Immunosuppressive Agents/pharmacology , Induced Pluripotent Stem Cells/immunology , Living Donors
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