Stem Cells
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First published online October 12, 2006
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2006-0303v1
25/2/332    most recent
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Submitted on May 22, 2006
Accepted on October 6, 2006

Tissue-Specific Stem Cells

Distinct population of hair cell progenitors can be isolated from the postnatal mouse cochlea using side population analysis

Etienne Savary 1, Jean Philippe Hugnot 1, Yolaine Chassigneux 1, Cecile Travo 1, Christophe Duperray 2, Thomas Van De Water 3, Azel Zine 1*

1 INSERM UMR 583, Institute of Neuroscience, University Montpellier 1, Montpellier, France
2 Institute of Research in Biotherapy, CHU Montpellier, Montpellier, France
3 University of Miami Ear Institute, University of Miami Miller School of Medicine, Miami, Florida

* To whom correspondence should be addressed. E-mail: zine{at}montp.inserm.fr.


  Abstract

In mammals, the permanence of hearing loss is mostly due to the incapacity of the cochlea to replace lost mechano-receptor cells, i.e. hair cells (HCs). The generation of new HCs from a renewable source of progenitors is a principal requirement for developing a cell therapy within this sensory organ. A subset of stem cells, termed 'side population' (SP) has been identified in several tissues of mammals. The ATP-binding cassette transporter Abcg2/Bcrp1 contributes to the specification of the SP phenotype and is proposed as a universal marker for stem/progenitor cells. A defining character of these SP cells is a high efflux capacity for Hoechst dye.

Here, we demonstrate that Abcg2 transporter is expressed with two other stem/progenitor cell markers (i.e. Nestin and Musashi1) in distinct and overlapping domains of the supporting cells within the postnatal cochlea.

We have developed and describe a fluorescence activated cell sorter (FACS) technique that enables the purification of a discrete subpopulation of SP-supporting cells from the early postnatal mouse cochlea based on their ability to exclude Hoechst dye.

These FACS isolated cells can divide and express markers of stem/progenitor cells such as Abcg2 a determinant of the SP phenotype and Musashi1, a neural stem/progenitor cell marker. These markers can differentiate cells expressing markers of HCs and supporting cells in vitro. Our observation that these SP cells are capable of differentiating into hair cell-like cells implies a possible use for such cells, i.e. the replacement of lost auditory HCs within damaged cochlea.

 Key Words. hearing loss, hair cells, Abcg2 transporter, stem/progenitor cells, side population, SP-supporting cells






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