Document Detail


Stem/progenitor cells derived from the cochlear sensory epithelium give rise to spheres with distinct morphologies and features.
MedLine Citation:
PMID:  19247714     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent the most suitable sphere type for cell-based assays or animal model transplantation studies aimed at development of cell replacement therapies.
Authors:
Marc Diensthuber; Kazuo Oshima; Stefan Heller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-02-27
Journal Detail:
Title:  Journal of the Association for Research in Otolaryngology : JARO     Volume:  10     ISSN:  1438-7573     ISO Abbreviation:  J. Assoc. Res. Otolaryngol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-04-28     Completed Date:  2009-07-15     Revised Date:  2011-02-04    
Medline Journal Info:
Nlm Unique ID:  100892857     Medline TA:  J Assoc Res Otolaryngol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-90     Citation Subset:  IM    
Affiliation:
Departments of Otolaryngology-Head & Neck Surgery and Molecular & Cellular Physiology, School of Medicine, Stanford University, 801 Welch Road, Stanford, CA 94305-5739, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / biosynthesis
Cell Culture Techniques
Cell Differentiation*
Cell Proliferation
Cochlea / cytology*,  metabolism
Epithelium / anatomy & histology*,  metabolism
Homeodomain Proteins / biosynthesis
Immunohistochemistry
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
PAX2 Transcription Factor / biosynthesis
Stem Cells / cytology*,  metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
DC006167/DC/NIDCD NIH HHS; R01 DC006167-01/DC/NIDCD NIH HHS; R01 DC006167-02/DC/NIDCD NIH HHS; R01 DC006167-03/DC/NIDCD NIH HHS; R01 DC006167-04/DC/NIDCD NIH HHS; R01 DC006167-05/DC/NIDCD NIH HHS; R01 DC006167-06/DC/NIDCD NIH HHS; R01 DC006167-07A2/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Cadherins; 0/Homeodomain Proteins; 0/PAX2 Transcription Factor; 0/Pax2 protein, mouse; 0/insulin gene enhancer binding protein Isl-1
Comments/Corrections

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