MP19-13 DEVELOPMENT OF A LARGE XENOGRAFT ANIMAL MODEL TO INVSTIGATE EFFICACY OF CELL-BASED THERAPIES TO TREAT STRESS URINARY INCONTINENCE

Abstract

You have accessJournal of UrologyStem Cell Research1 Apr 2015MP19-13 DEVELOPMENT OF A LARGE XENOGRAFT ANIMAL MODEL TO INVSTIGATE EFFICACY OF CELL-BASED THERAPIES TO TREAT STRESS URINARY INCONTINENCE Bastian Amend, Alexandra Kelp, Martin Vaegler, Arnulf Stenzl, and Karl-Dietrich Sievert Bastian AmendBastian Amend More articles by this author , Alexandra KelpAlexandra Kelp More articles by this author , Martin VaeglerMartin Vaegler More articles by this author , Arnulf StenzlArnulf Stenzl More articles by this author , and Karl-Dietrich SievertKarl-Dietrich Sievert More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1005AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Currently, a functional cure for stress urinary incontinence (SUI) does not exist. The only feasible treatment is to ameliorate symptoms. Application of regeneration-competent progenitor or stem cells could possibly restore function of the rhabdosphincter. This study aims to develop a large animal model that incorporates safe, yet precise cell injection technologies, to investigate localization, distribution, survival, and possible integration of human mesenchymal stromal cells (MSC) after injection in the bladder sphincter muscle of minipigs. METHODS Undifferentiated different human MSC (bone marrow, placenta or adipose tissue) were injected into the rhabdosphincter (4 depots,2x106 cells in total) by transurethral-guided needle injection. Seventy-two immune-supressed female minipigs were divided into 12 groups with six animals each: 3 groups of MSC populations consisting of 4 follow-up points (3w,3m,6m,and 12m). Sham (24) underwent treatment with culture media. Functional regeneration of rhabdosphincter was evaluated by urodynamic urethral pressure profile(UPP) at above mentioned follow-up. The rhabdosphincter was harvested for further investigation. General histology was performed at the localization, distribution of MSC on cryostat sections as well as TUNEL-staining for the apoptosis rate. RESULTS Prior to initial MSC treatment, all animals received an MSC treatment Cyclosporine®(15mg/kg, iv) and continued orally post-operatively. Six did not survive; 5 from sham group and 1 that received cells. All animals tested (n=59/72) did not demonstrate signs of human MSC rejection nor inflammation. Only in 1/59, a fibrotic encapsulation of MSC injected was observed. The 59 urodynamic-investigated pigs demonstrated a functional increased UPP compared to sham without differences related to MSC source. During all tested evaluation points, cells remained in the region of injection without migration and/or disappearance. Over time the depots appeared to decrease. Throughout the investigation, apoptosis was present in ≤10% of injected MCS locations according to TUNEL-staining in the depots, whereas the host tissue had an average apoptosis of 2%. CONCLUSIONS Immune-supressed minipigs served as a model in preclinical cell therapy studies. Transurethral needle injection of human MSC is feasible and potential minimal-invasive application technique for clinical regeneration of injured and degenerated rhabdosphincter in the future, given that injected cells survived and effected functional regeneration. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e220 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bastian Amend More articles by this author Alexandra Kelp More articles by this author Martin Vaegler More articles by this author Arnulf Stenzl More articles by this author Karl-Dietrich Sievert More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...