Abstract
Cholesteatoma is a potentially life-threatening middle ear lesion due to the formation of an inflamed ectopic mass of keratinizing squamous epithelium. Surgical removal remains the only treatment option, emphasizing the need to gain a better understanding of this severe disease. We show for the first time that stem cells residing in cholesteatoma tissue contribute to disease progression. Cells expressing the “stemness” markers Nestin and S100B were detected in middle ear cholesteatoma and auditory canal skin. Isolated Nestin + /S100B + -cells showed the capability for self-renewal, neurosphere formation and differentiation into mesodermal and ectodermal cell types. Compared to auditory canal skin stem cells middle ear cholesteatoma-derived stem cells displayed an enhanced susceptibility to inflammatory stimuli, and this suggested a possible contribution to the inflammatory environment in cholesteatoma tissue. Cholesteatoma derived stem cells were able to differentiate into keratinocyte-like cells using factors mimicking the microenvironment of cholesteatoma. Our findings demonstrate a new perspective on the pathogenesis of cholesteatoma and may lead to new treatment strategies for this severe middle ear lesion.
Highlights
Cholesteatoma is an expanding lesion of the middle ear, consisting of stratified keratinizing squamous epithelium
Cells expressing the stem cell marker Nestin are present in middle ear cholesteatoma tissue and auditory canal skin
We investigated morphology using Haematoxylin and Eosin (H&E) staining, and we demonstrated the characteristic epithelial layer and lamina propria of the auditory canal skin (Fig. 1B) as well as the characteristic structures of matrix (M), perimatrix (P), and cystic contents (C) in cholesteatoma tissue (Fig. 1C)
Summary
Cholesteatoma is an expanding lesion of the middle ear, consisting of stratified keratinizing squamous epithelium. The formation involves migration of stem cells from bone marrow and the vascular wall into the lesion[12]. To investigate their potential role in the middle ear cholesteatoma, we analyzed cholesteatoma tissue and auditory canal skin for the presence of stem cells. For the first time, the presence of a stem cell population in cholesteatoma tissue and auditory canal skin. Factors present in the middle ear cholesteatoma microenvironment were able to differentiate the cholesteatoma-derived stem cells into epidermal cell types
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