Previous Article |
Table of Contents
| Next Article 
From The Cover
Medical Sciences
Generation of hair cells by stepwise differentiation of embryonic stem cells
Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114
Edited by A. James Hudspeth, The Rockefeller University, New York, NY, and approved September 17, 2003 (received for review July 17, 2003)
The increase in life expectancy is accompanied by the growing burden of chronic diseases. Hearing loss is perhaps the most prevalent of all chronic diseases. In addition to age-related hearing loss, a substantial number of cases of audiological impairment are either congenital in nature or acquired during childhood. The permanence of hearing loss is mainly due to the inability of the cochlear sensory epithelium to replace lost mechanoreceptor cells, or hair cells. Generation of hair cells from a renewable source of progenitors that can be transplanted into damaged inner ears is a principal requirement for potential cell replacement therapy in this organ. Here, we present an experimental protocol that enables us to routinely create inner ear progenitors from murine embryonic stem cells in vitro. These progenitors express a comprehensive set of marker genes that define the developing inner ear, in particular the organ's developing sensory patches. We further demonstrate that cells that express markers characteristic of hair cells differentiate from embryonic stem cell-derived progenitors. Finally, we show that these progenitors integrate into the developing inner ear at sites of epithelial injury and that integrated cells start expressing hair cell markers and display hair bundles when situated in cochlear or vestibular sensory epithelia in vivo.
Abbreviations: ES, embryonic stem; EGF, epidermal growth factor; IGF-1, insulin-like growth factor 1; bFGF, basic fibroblast growth factor; 
-gal, -galactosidase.
* Present address: University Hospital of Wales, Heath Park, Cardiff CF14 4XW, Wales.
To whom correspondence should be addressed. E-mail: hellers{at}epl.meei.harvard.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
This article has been cited by other articles in HighWire Press-hosted journals:
|
|
 |
|
  Z. Hu and J. T. Corwin Inner ear hair cells produced in vitro by a mesenchymal-to-epithelial transition PNAS, October 16, 2007; 104(42): 16675 - 16680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Kelley Has hair cell loss MET its match? PNAS, October 16, 2007; 104(42): 16400 - 16401. [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Doyle, A. Kazda, Y. Hort, S. M. McKay, and S. Oleskevich Differentiation of Adult Mouse Olfactory Precursor Cells into Hair Cells In Vitro Stem Cells, March 1, 2007; 25(3): 621 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. de Magalhaes and G. M. Church Genomes Optimize Reproduction: Aging as a Consequence of the Developmental Program Physiology, August 1, 2005; 20(4): 252 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Hawkins and M. Lovett The developmental genetics of auditory hair cells Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R289 - R296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Barald and M. W. Kelley From placode to polarization: new tunes in inner ear development Development, September 1, 2004; 131(17): 4119 - 4130. [Abstract] [Full Text] [PDF]
|
|
