Stem cells in middle ear cholesteatoma contribute to its pathogenesis.

Nagel J, Wöllner S, Schürmann M, Brotzmann V, Müller J, Greiner J, Goon P, Kaltschmidt B, Kaltschmidt C, Sudhoff H (2018)
Nature Scientific Reports 8(1): 6204.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Nagel, Julia; Wöllner, Saskia; Schürmann, Matthias; Brotzmann, Viktoria; Müller, Janine; Greiner, JohannesUniBi ; Goon, Peter; Kaltschmidt, BarbaraUniBi; Kaltschmidt, ChristianUniBi; Sudhoff, HolgerUniBi
Abstract / Bemerkung
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.
Nature Scientific Reports
Page URI


Nagel J, Wöllner S, Schürmann M, et al. Stem cells in middle ear cholesteatoma contribute to its pathogenesis. Nature Scientific Reports. 2018;8(1): 6204.
Nagel, J., Wöllner, S., Schürmann, M., Brotzmann, V., Müller, J., Greiner, J., Goon, P., et al. (2018). Stem cells in middle ear cholesteatoma contribute to its pathogenesis. Nature Scientific Reports, 8(1), 6204.
Nagel, J., Wöllner, S., Schürmann, M., Brotzmann, V., Müller, J., Greiner, J., Goon, P., Kaltschmidt, B., Kaltschmidt, C., and Sudhoff, H. (2018). Stem cells in middle ear cholesteatoma contribute to its pathogenesis. Nature Scientific Reports 8:6204.
Nagel, J., et al., 2018. Stem cells in middle ear cholesteatoma contribute to its pathogenesis. Nature Scientific Reports, 8(1): 6204.
J. Nagel, et al., “Stem cells in middle ear cholesteatoma contribute to its pathogenesis.”, Nature Scientific Reports, vol. 8, 2018, : 6204.
Nagel, J., Wöllner, S., Schürmann, M., Brotzmann, V., Müller, J., Greiner, J., Goon, P., Kaltschmidt, B., Kaltschmidt, C., Sudhoff, H.: Stem cells in middle ear cholesteatoma contribute to its pathogenesis. Nature Scientific Reports. 8, : 6204 (2018).
Nagel, Julia, Wöllner, Saskia, Schürmann, Matthias, Brotzmann, Viktoria, Müller, Janine, Greiner, Johannes, Goon, Peter, Kaltschmidt, Barbara, Kaltschmidt, Christian, and Sudhoff, Holger. “Stem cells in middle ear cholesteatoma contribute to its pathogenesis.”. Nature Scientific Reports 8.1 (2018): 6204.

42 References

Daten bereitgestellt von Europe PubMed Central.

Bhutta MF, Williamson IG, Sudhoff HH., BMJ 342(), 2011
PMID: 21372073
Pediatric middle ear cholesteatoma: the comparative study of congenital cholesteatoma and acquired cholesteatoma.
Morita Y, Yamamoto Y, Oshima S, Takahashi K, Takahashi S., Eur Arch Otorhinolaryngol 273(5), 2015
PMID: 26044405
The contralateral ear in cholesteatoma.
da Costa SS, Teixeira AR, Rosito LP., Eur Arch Otorhinolaryngol 273(7), 2015
PMID: 26223352
Updates and knowledge gaps in cholesteatoma research.
Kuo CL, Shiao AS, Yung M, Sakagami M, Sudhoff H, Wang CH, Hsu CH, Lien CF., Biomed Res Int 2015(), 2015
PMID: 25866816
Molecular biology of cholesteatoma.
Maniu A, Harabagiu O, Perde Schrepler M, Catana A, Fanuta B, Mogoanta CA., Rom J Morphol Embryol 55(1), 2014
PMID: 24715159
Notes on the microbiology of cholesteatoma: clinical findings and treatment.
Ricciardiello F, Cavaliere M, Mesolella M, Iengo M., Acta Otorhinolaryngol Ital 29(4), 2009
PMID: 20161877
Etiopathogenesis of cholesteatoma.
Olszewska E, Wagner M, Bernal-Sprekelsen M, Ebmeyer J, Dazert S, Hildmann H, Sudhoff H., Eur Arch Otorhinolaryngol 261(1), 2003
PMID: 12835944
Contemporary assessment and management of congenital cholesteatoma.
Richter GT, Lee KH., Curr Opin Otolaryngol Head Neck Surg 17(5), 2009
PMID: 19745736
Isolation and characterization of multipotent mesenchymal stem cells in nasal polyps.
Cho JS, Park JH, Kang JH, Kim SE, Park IH, Lee HM., Exp. Biol. Med. (Maywood) 240(2), 2014
PMID: 25294891
Tissue-specific somatic stem-cell isolation and characterization from human endometriosis. Key roles in the initiation of endometrial proliferative disorders.
Heidari-Keshel S, Rezaei-Tavirani M, Ai J, Soleimani M, Baradaran-Rafii A, Ebrahimi M, Roozafzoon R, Rahmanzadeh S, Raeisossadati R, Omidi R, Ghanbari Z., Minerva Med. 106(2), 2014
PMID: 25517500
Functional role of matrix metalloproteinase-8 in stem/progenitor cell migration and their recruitment into atherosclerotic lesions.
Xiao Q, Zhang F, Lin L, Fang C, Wen G, Tsai TN, Pu X, Sims D, Zhang Z, Yin X, Thomaszewski B, Schmidt B, Mayr M, Suzuki K, Xu Q, Ye S., Circ. Res. 112(1), 2012
PMID: 23071158
DNA analysis of human cholesteatomas.
Desloge RB, Carew JF, Finstad CL, Steiner MG, Sassoon J, Levenson MJ, Staiano-Coico L, Parisier SC, Albino AP., Am J Otol 18(2), 1997
PMID: 9093669
Expression of toll-like receptors in chronic otitis media and cholesteatoma.
Hirai H, Kariya S, Okano M, Fukushima K, Kataoka Y, Maeda Y, Nishizaki K., Int. J. Pediatr. Otorhinolaryngol. 77(5), 2013
PMID: 23380629
Isolation of novel multipotent neural crest-derived stem cells from adult human inferior turbinate.
Hauser S, Widera D, Qunneis F, Muller J, Zander C, Greiner J, Strauss C, Luningschror P, Heimann P, Schwarze H, Ebmeyer J, Sudhoff H, Arauzo-Bravo MJ, Greber B, Zaehres H, Scholer H, Kaltschmidt C, Kaltschmidt B., Stem Cells Dev. 21(5), 2012
PMID: 22128806
Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics.
Greiner JF, Hauser S, Widera D, Muller J, Qunneis F, Zander C, Martin I, Mallah J, Schuetzmann D, Prante C, Schwarze H, Prohaska W, Beyer A, Rott K, Hutten A, Golzhauser A, Sudhoff H, Kaltschmidt C, Kaltschmidt B., Eur Cell Mater 22(), 2011
PMID: 22179938
Cholesteatoma-associated fibroblasts modulate epithelial growth and differentiation through KGF/FGF7 secretion.
Raffa S, Leone L, Scrofani C, Monini S, Torrisi MR, Barbara M., Histochem. Cell Biol. 138(2), 2012
PMID: 22481617
Establishment and characterization of an in vitro model for cholesteatoma.
Raynov AM, Choung YH, Park HY, Choi SJ, Park K., Clin Exp Otorhinolaryngol 1(2), 2008
PMID: 19434278
Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
Yoshikawa M, Kojima H, Yaguchi Y, Okada N, Saito H, Moriyama H., PLoS ONE 8(6), 2013
PMID: 23826119
Sphere-forming capacity as an enrichment strategy for epithelial-like stem cells from equine skin.
Borena BM, Meyer E, Chiers K, Martens A, Demeyere K, Broeckx SY, Duchateau L, Spaas JH., Cell. Physiol. Biochem. 34(4), 2014
PMID: 25277113
An in vitro growth study on cholesteatoma and normal skin.
Cheshire IM, Blight A, Proops DW., Clin Otolaryngol Allied Sci 20(5), 1995
PMID: 8582080
Co-expression of different angiogenic factors in external auditory canal cholesteatoma.
Naim R, Riedel F, Gotte K, Bran G, Sadick H, Gossler U, Hormann K., Acta Otolaryngol. 124(5), 2004
PMID: 15267172

Paracrine loops of keratinocyte stimulation in cholesteatoma tissue: an immunofluorescence, transmission electron microscopy, and molecular study.
d'Alessandro F, Raffa S, Mure C, Kovacs D, Torrisi MR, Barbara M., Otol. Neurotol. 31(7), 2010
PMID: 20679958
Expression of messenger RNA for keratinocyte growth factor in human cholesteatoma.
Kojima H, Matsuhisa A, Shiwa M, Kamide Y, Nakamura M, Ohno T, Moriyama H., Arch. Otolaryngol. Head Neck Surg. 122(2), 1996
PMID: 8630209
Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: differentiation response distinguishes KGF from EGF family.
Marchese C, Rubin J, Ron D, Faggioni A, Torrisi MR, Messina A, Frati L, Aaronson SA., J. Cell. Physiol. 144(2), 1990
PMID: 1696274
Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation.
Gibbs S, Silva Pinto AN, Murli S, Huber M, Hohl D, Ponec M., Wound Repair Regen 8(3), 2000
PMID: 10886810
In vivo over-expression of KGF mimic human middle ear cholesteatoma.
Yamamoto-Fukuda T, Akiyama N, Shibata Y, Takahashi H, Ikeda T, Koji T., Eur Arch Otorhinolaryngol 272(10), 2014
PMID: 25138153
The development of the mammalian outer and middle ear.
Anthwal N, Thompson H., J. Anat. 228(2), 2015
PMID: 26227955
[Epidermal stem cells in the tympanic membrane].
Wang WQ, Wang ZM, Tian J., Zhonghua Er Bi Yan Hou Ke Za Zhi 39(12), 2004
PMID: 15813011

SW, Sci Rep 5(), 2015
Localization of progenitor/stem cells in the human tympanic membrane.
Knutsson J, von Unge M, Rask-Andersen H., Audiol. Neurootol. 16(4), 2010
PMID: 21051884
Endothelial progenitor cells populate the stromal stem niche of tympanum.
Rusu MC, Manoiu VS, Popescu VM, Ciuluvica RC., Folia Morphol. (Warsz) (), 2017
PMID: 28553861
Epidermal stem cells.
Janes SM, Lowell S, Hutter C., J. Pathol. 197(4), 2002
PMID: 12115864
1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis.
Sudhoff H, Klenke C, Greiner JF, Muller J, Brotzmann V, Ebmeyer J, Kaltschmidt B, Kaltschmidt C., PLoS ONE 10(7), 2015
PMID: 26207629
Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.
Muller J, Ossig C, Greiner JF, Hauser S, Fauser M, Widera D, Kaltschmidt C, Storch A, Kaltschmidt B., Stem Cells Transl Med 4(1), 2014
PMID: 25479965


Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®


PMID: 29670222
PubMed | Europe PMC

Suchen in

Google Scholar