Identification of different phenotypes of interstitial cells in the upper and deep lamina propria of the human bladder dome

Abstract

Purpose: There is increasing evidence for an important role of the lamina propria in bladder physiology and interstitial cells seem to have a key role in this area. Interstitial cells in the upper lamina propria have been studied most frequently. We characterized interstitial cells in the deeper lamina propria and hypothesized that the 2 interstitial cell populations have different phenotypes based on their ultrastructural and immunohistochemical properties.

Materials and methods: Tissue samples were obtained from macroscopically and microscopically normal areas of radical cystectomy specimens. A panel of immunohistochemical markers was used to characterize lamina propria interstitial cells. Single/double immunohistochemistry/immunofluorescence was performed. At a second phase electron microscopy was used to compare upper and deeper lamina propria interstitial cells.

Results: Overall the phenotype of upper lamina propria interstitial cells was vimentin, α-smooth muscle actin, caveolin-1 and 2, PDGFRα, and nonphosphorylated and phosphorylated connexin 43 positive, and CD34 and c-kit negative. The overall phenotype of deeper lamina propria interstitial cells was vimentin, CD34 and nonphosphorylated connexin 43 positive, and α-smooth actin, caveolin-1 and 2, PDGFRα, phosphorylated connexin 43 and c-kit negative. Based on ultrastructural findings upper lamina propria interstitial cells were fibroblasts with myoid features and sparse myofibroblasts while deeper lamina propria interstitial cells were interstitial cell of Cajal-like cells.

Conclusions: To our knowledge this is the first study of 2 main interstitial cell populations in the upper and deeper lamina propria of the human bladder with distinct ultrastructural and immunohistochemical phenotypes. Future research is needed to elucidate whether these morphological findings reflect different roles for upper and deeper lamina propria interstitial cells in bladder physiology.

Keywords: fibroblasts; interstitial cells of Cajal; mucous membrane; phenotype; urinary bladder.