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

Frank Mattias Schäfer, Khalid Algarrahi, Alyssa Savarino, Xuehui Yang, Catherine Seager, Debra Franck, Kyle Costa, Shanshan Liu, Tanya Logvinenko, Rosalyn Adam, Joshua R. Mauney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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. In this article, Mauney and colleagues show the source of urothelial progenitors utilized during bladder regeneration is dependent on the nature of injury. Fate-mapping experiments reveal that host basal and intermediate cell progeny differentially contribute to de novo urothelial formation in bladder augmentation and mucosal resection settings. These results highlight the diversity of urothelial regenerative responses to surgical injury.

Original languageEnglish (US)
Pages (from-to)2005-2017
Number of pages13
JournalStem cell reports
Volume9
Issue number6
DOIs
StatePublished - Dec 12 2017

Keywords

  • bladder
  • progenitor
  • tissue engineering
  • urothelium

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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