Mode of Surgical Injury Influences the Source of Urothelial Progenitors during Bladder Defect Repair

Stem Cell Reports. 2017 Dec 12;9(6):2005-2017. doi: 10.1016/j.stemcr.2017.10.025. Epub 2017 Nov 22.

Abstract

The bladder urothelium functions as a urine-blood barrier and consists of basal, intermediate, and superficial cell populations. Reconstructive procedures such as augmentation cystoplasty and focal mucosal resection involve localized surgical damage to the bladder wall whereby focal segments of the urothelium and underlying submucosa are respectively removed or replaced and regeneration ensues. We demonstrate using lineage-tracing systems that urothelial regeneration following augmentation cystoplasty with acellular grafts exclusively depends on host keratin 5-expressing basal cells to repopulate all lineages of the de novo urothelium at implant sites. Conversely, repair of focal mucosal defects not only employs this mechanism, but in parallel host intermediate cell daughters expressing uroplakin 2 give rise to themselves and are also contributors to superficial cells in neotissues. These results highlight the diversity of urothelial regenerative responses to surgical injury and may lead to advancements in bladder tissue engineering approaches.

Keywords: bladder; progenitor; tissue engineering; urothelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cell Tracking / methods
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Intraoperative Complications / metabolism
  • Intraoperative Complications / pathology
  • Keratin-5 / genetics*
  • Mice
  • Regeneration / genetics*
  • Tissue Engineering
  • Urinary Bladder / growth & development*
  • Urinary Bladder / injuries
  • Urinary Bladder / metabolism
  • Urine / physiology
  • Uroplakin II / genetics*
  • Urothelium / growth & development*
  • Urothelium / injuries
  • Urothelium / metabolism

Substances

  • Keratin-5
  • Uroplakin II