Neuronal Differentiation Capability of Nasal Polyps of Chronic Rhinosinusitis

Arch Immunol Ther Exp (Warsz). 2017 Oct;65(5):431-443. doi: 10.1007/s00005-017-0456-8. Epub 2017 Mar 9.

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.

Keywords: Chronic rhinosinusitis with nasal polyps; Nasal polyps; Neuronal differentiation; Stem cells.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cell Self Renewal*
  • Cells, Cultured
  • Chronic Disease
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Intermediate Filaments / genetics
  • Intermediate Filaments / metabolism
  • Kruppel-Like Factor 4
  • Male
  • Middle Aged
  • Nasal Polyps / diagnosis
  • Nasal Polyps / immunology*
  • Nestin / genetics
  • Nestin / metabolism
  • Neurogenesis
  • Octamer Transcription Factor-3 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rhinitis / diagnosis
  • Rhinitis / immunology*
  • Sinusitis / diagnosis
  • Sinusitis / immunology*
  • Stem Cell Niche / physiology*
  • Stem Cells / physiology*
  • Transcriptome

Substances

  • KLF4 protein, human
  • Klf4 protein, rat
  • Kruppel-Like Factor 4
  • Nestin
  • Octamer Transcription Factor-3
  • Granulocyte-Macrophage Colony-Stimulating Factor