MP8-02 CHARACTERIZATION OF THE MURINE BLADDER RESPONSE TO SUBTOTAL CYSTECTOMY: A MODEL OF MAMMALIAN ORGAN REGENERATION

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 2015MP8-02 CHARACTERIZATION OF THE MURINE BLADDER RESPONSE TO SUBTOTAL CYSTECTOMY: A MODEL OF MAMMALIAN ORGAN REGENERATION Grace Delos Santos, Andrew Flum, Natalie Kukulka, Robert Dettman, and Edward Gong Grace Delos SantosGrace Delos Santos More articles by this author , Andrew FlumAndrew Flum More articles by this author , Natalie KukulkaNatalie Kukulka More articles by this author , Robert DettmanRobert Dettman More articles by this author , and Edward GongEdward Gong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.269AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder dysfunction is a significant source of urinary incontinence. Regeneration of adult bladders has been proposed to restore function. However the molecular mechanisms that mediate bladder regeneration are unknown. Regeneration of the rat bladder was reported in the literature, but rats, as a model, do not allow us to use the sophisticated genetic tools that are available in mice. We therefore investigated how mouse bladders regenerated after subtotal cystectomy (STC). METHODS STC (removal of 50% of the bladder) was performed on adult female CD1 mice. Mice that underwent low-midline laparotomy served as controls. Voiding stains on paper (VSOP) and urodynamics were used to demonstrate bladder function. Bladders were harvested at 1, 2, 4, and 8 weeks. Masson's trichrome stain identified collagen, as a proxy for bladder fibrosis. Immunohistochemistry expression of cytokeratin-5, smooth muscle myosin, and smooth muscle actin identified differentiated cells. Phospho-Histone H3 identified mitotically active cells. The movement of cells that divided during days 3–7 days post-STC was tracked using ethynyl deoxyuridine (EdU). RESULTS The STC group did not reach the same mean voided volumes as controls (Figure 1), with the majority of volume restoration occurring within the first two weeks. On cystometry, the STC bladders had higher filling pressure and higher maximum voiding pressures. Regenerating bladders had thinner walls with less mean muscle thickness, and they showed increased collagen deposition at the incision as well as throughout the bladder wall. Cell populations differed in their response to injury. Urothelial regeneration was observed by day 7. Urothelial cells incorporated EdU, indicating that they proliferated soon after STC. Smooth muscle cells represented only a small percentage of EdU+ cells indicating that smooth muscle growth was limited in the first week despite bladder volume increase. CONCLUSIONS Regeneration occurs in the adult mouse bladder, but is mostly limited to the urothelium. Though bladder volume increases after STC this appears to be as a result of tissue remodeling and not muscle regeneration. This tissue remodeling closely resembles bladder fibrosis. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e73-e74 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Grace Delos Santos More articles by this author Andrew Flum More articles by this author Natalie Kukulka More articles by this author Robert Dettman More articles by this author Edward Gong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...