Stem/Progenitor Cells Derived from the Cochlear Sensory Epithelium Give Rise to Spheres with Distinct Morphologies and Features |
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Authors: | Marc Diensthuber Kazuo Oshima Stefan Heller |
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Affiliation: | 1.Departments of Otolaryngology–Head & Neck Surgery and Molecular & Cellular Physiology, School of Medicine, Stanford University, 801 Welch Road, Stanford, CA 94305-5739 USA ;2.Department of Otorhinolaryngology, Hannover Medical University, Carl-Neuberg-Straße 1, 30625 Hannover, Germany |
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Abstract: | 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. |
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Keywords: | inner ear regeneration hair cell supporting cell organ of Corti stem cell |
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