title: Induction of differentiation of human embryonic stem cells into functional hair-cell-like cells in the absence of stromal cells.
abstract: Sensorineural hearing loss and vestibular dysfunction have become the most common forms of sensory defects. Stem cell-based therapeutic strategies for curing hearing loss are being developed. Several attempts to develop hair cells by using chicken utricle stromal cells as feeder cells have resulted in phenotypic conversion of stem cells into inner ear hair-cell-like cells. Here, we induced the differentiation of human embryonic stem cells (hESCs) into otic epithelial progenitors (OEPs), and further induced the differentiation of OEPs into hair-cell-like cells using different substrates. Our results showed that OEPs cultured on the chicken utricle stromal cells with the induction medium could differentiate into hair-cell-like cells with stereociliary bundles. Co-culture with stromal cells, however, may be problematic for subsequent examination of the induced hair-cell-like cells. In order to avoid the interference from stromal cells, we cultured OEPs on laminin with different induction media and examined the effects of the induction medium on the differentiation potentials of OEPs into hair-cell-like cells. The results revealed that the culture of OEPs on laminin with the conditioned medium from chicken utricle stromal cells supplemented with EGF and all-trans retinoic acid (RA) could promote the organization of cells into epithelial clusters displaying hair-cell-like cells with stereociliary bundles. These cells also displayed the expected electrophysiological properties.
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China; College of Life Sciences, Guizhou University, Guiyang 550025, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, The Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, PR China.
authors.forename: Haosong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China; Departments of Cell Biology and Otolaryngology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zhejiang University, Hangzhou 310058, PR China. Electronic address: wjfu@zju.edu.cn.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002645:Chickens; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008938:Mitosis; D012444:Saccule and Utricle / Q000166:cytology
chemical_list: D007797:Laminin
keywords: Differentiation; Electrophysiological property; Hair-cell-like cells; Human embryonic stem cells; Progenitor cells; Stereociliary bundles