Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy

Mona Zarifpour, Karl Erik Andersson, Sneha S. Kelkar, Aaron M Mohs, Cathy Mendelsohn, Kerry Schneider, Frank Marini, George J. Christ

Research output: Contribution to journalArticle

Abstract

Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC) in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T2-weighted magnetic resonance imaging (MRI). Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC) following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks) post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume), consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers) of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalBioResearch Open Access
Volume6
Issue number1
DOIs
StatePublished - May 2017

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Keywords

  • bladder
  • murine
  • regeneration
  • repair
  • subtotal cystectomy
  • wound healing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Zarifpour, M., Andersson, K. E., Kelkar, S. S., Mohs, A. M., Mendelsohn, C., Schneider, K., Marini, F., & Christ, G. J. (2017). Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy. BioResearch Open Access, 6(1), 35-45. https://doi.org/10.1089/biores.2017.0011