MP61-16 PRE-CLINICAL AND CLINICAL TRANSLATION OF A TISSUE ENGINEERED NEO−URINARY CONDUIT USING ADIPOSE DERIVED SMOOTH MUSCLE CELLS FOR URINARY RECONSTRUCTION

You have accessJournal of UrologyBladder Cancer: Invasive IV1 Apr 2014MP61-16 PRE-CLINICAL AND CLINICAL TRANSLATION OF A TISSUE ENGINEERED NEO−URINARY CONDUIT USING ADIPOSE DERIVED SMOOTH MUSCLE CELLS FOR URINARY RECONSTRUCTION Trinity Bivalacqua, Gary Steinberg, Norm Smith, Seth Lerner, Bernie Bochner, Cheryl Lee, Elias Rivera, Deepak Jain, Timothy Bertram, and Mark Schoenberg Trinity BivalacquaTrinity Bivalacqua More articles by this author , Gary SteinbergGary Steinberg More articles by this author , Norm SmithNorm Smith More articles by this author , Seth LernerSeth Lerner More articles by this author , Bernie BochnerBernie Bochner More articles by this author , Cheryl LeeCheryl Lee More articles by this author , Elias RiveraElias Rivera More articles by this author , Deepak JainDeepak Jain More articles by this author , Timothy BertramTimothy Bertram More articles by this author , and Mark SchoenbergMark Schoenberg More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1893AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Surgical treatment of muscle−invasive bladder cancer is radical cystectomy with urinary reconstruction using gastrointenstinal segments which can result in infectious, mechanical and metabolic complications. As an alternative, diversion composed of non-absorptive urinary tissue from a product known as Neo−Urinary Conduit (NUC) has been developed. NUC is produced by seeding autologous smooth muscle cells (SMC) onto a biodegradable PLGA scaffold. We provide histological assessment of results from animals showing the regenerative outcomes and compare to results from conduits explanted 7 weeks and 10 months post-implantation from two patients enrolled in a Phase 1 clinical trial. METHODS SMC were isolated from fat, ex vivo expanded, and grown on biodegradable scaffold. The porcine model involved ureteral implantation into a scaffold lined with SMC. The NUC was wrapped intraoperatively with omentum or peritoneum to provide a blood supply for tissue regeneration. The same technique was performed in patients after radical cystectomy. Seven patients have undergone implantation with 4 explants to date. Analysis of regenerated tissue using histomorphology and immunohistochemical markers for urothelium (cytokeratin 7), epithelium, (cytokeratin AE1/AE3), nerve (neurofilament 160) and smooth muscle (calponin 1) was performed. RESULTS NUC implantation in pigs results in regenerated tissue 3 months after implantation with formation of urinary tissue. Lumen was covered by urothelium (CK7+) and smooth muscle bundles (calponin +) were visualized and observed in the proximal and mid segments of NUC. In the phase 1 clinical trial, 7−weeks post implantation, human explant showed evidence of urothelium(CK7+) and epithelium (AE1/AE3) throughout the NUC, followed by non−layered smooth muscle cells (calponin +) in remaining body of NUC. At 10−months post−implantation a mature organ composed of urothelium and tunica muscularis layer were fully developed and characterized by the presence of layered smooth muscle bundles of the regenerated conduit wall. There was innervation (neurofilament 160) of NUC from native ureters. CONCLUSIONS The findings in human explants are consistent with the histological findings from the translational porcine model and support the use of AD−derived SMC seeded onto a scaffold to provide an innate regenerative response in a Phase 1 first in human clinical trial. The development of a clinically functional urinary conduit remains to be proven in an ongoing multi-center phase 1 clinical trial. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e689 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Trinity Bivalacqua More articles by this author Gary Steinberg More articles by this author Norm Smith More articles by this author Seth Lerner More articles by this author Bernie Bochner More articles by this author Cheryl Lee More articles by this author Elias Rivera More articles by this author Deepak Jain More articles by this author Timothy Bertram More articles by this author Mark Schoenberg More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...