title: Neuronal Differentiation Capability of Nasal Polyps of Chronic Rhinosinusitis.
abstract: Chronic rhinosinusitis with nasal polyps is considered a subgroup of chronic rhinosinusitis and a significant health problem, but the pathogenesis remains unclear to date. Therefore, we investigated the stemness to determine the role of stem cells in nasal polyps, with additional analysis of the neuronal differentiation potential of nasal polyp cells. We determined gene and protein expression profiles of stem cells in nasal polyp tissues, using whole genome microarray, quantitative real-time PCR (qPCR), immunohistochemistry, and flow cytometry. To evaluate the neuronal differentiation potential of nasal polyp cells, we used an efficient xenogeneic co-culture model with unsliced adult rat brain biopsies, followed by qPCR, immunohistochemistry, and growth factor antibody arrays. During gene expression analysis and immunohistochemistry, we were able to detect different stem cell markers, like Oct-4, Sox2, Klf4, c-Myc, ABCG2, Nanog, CD133, and Nestin, which confirmed the existence of stem cell like cells within nasal polyps. In addition, co-culture experiments give evidence for a guided differentiation into the neuronal lineage by overexpression of Nestin, Neurofilament, and GM-CSF. Our study demonstrated the expression of stem cell-related markers in nasal polyps. Furthermore, we characterized, for the first time, the stemness and neuronal differentiation potential of nasal polyp cells. These results gave new insights into the pathogenesis of nasal polyps and its therapeutic effectiveness could represent a promising strategy in the future.
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. Michael.Koennecke@uksh.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Koennecke
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Böscke
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Pfannerstill
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reers
authors.affiliation: Fraunhofer Research Institution for Marine Biotechnology, EMB, Lübeck, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Elsner
authors.affiliation: Fraunhofer Research Institution for Marine Biotechnology, EMB, Lübeck, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fell
authors.affiliation: Fraunhofer Research Institution for Marine Biotechnology, EMB, Lübeck, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Richter
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Bruchhage
authors.affiliation: Fraunhofer Research Institution for Marine Biotechnology, EMB, Lübeck, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schumann
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Pries
authors.affiliation: Center for Rhinology and Allergology, Wiesbaden, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klimek
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Schleswig-Holstein, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007382:Intermediate Filaments / Q000235:genetics / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000175:diagnosis / Q000276:immunology*; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012220:Rhinitis / Q000175:diagnosis / Q000276:immunology*; D012852:Sinusitis / Q000175:diagnosis / Q000276:immunology*; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D059467:Transcriptome
chemical_list: C000715467:KLF4 protein, human; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D064231:Nestin; D050814:Octamer Transcription Factor-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Chronic rhinosinusitis with nasal polyps; Nasal polyps; Neuronal differentiation; Stem cells