US researchers won the first prize at the 29th Annual EAU Congress in Stockholm for Best Abstract in Non-Oncology. Lead author Trinity Bivalacqua (Baltimore, USA) and colleagues bagged the top prize for their work titled “Pre-clinical and clinical translation of a tissue engineered neo?urinary conduit using adipose derived smooth muscle cells for urinary reconstruction.”
Below is the unedited version of the prize-winning abstract:
Abstract Nr: AM14-3553: "Pre-clinical and clinical translation of a tissue engineered neo−urinary conduit using adipose derived smooth muscle cells for urinary reconstruction"
Authors: Bivalacqua, T.1, Steinberg, G.2, Smith, N2, Lerner, S.3, Bochner, B.4, Lee, C.5, Rivera, E.6, Jain, D.6, Bertram, T.6, Schoenberg, M.7
1Johns Hopkins Medical Institutions, Brady Urological Institute, Baltimore, United States of America, 2University of Chicago, Urology, Chicago, United States of America, 3Baylor College of Medicine, Urology, Dallas, United States of America, 4Memorial Sloan Kettering Cancer Center, Urology, New York, United States of America, 5University of Michigan, Urology, Michigan, United States of America, 6Tengion, Regenerative Medicine, Winston-Salem, United States of America, 7Johns Hopkins, Urology, Baltimore, United States of America
Introduction & Objectives
Surgical treatment of muscle−invasive bladder cancer is radical cystectomy with urinary reconstruction. Urinary diversion involves gastrointenstinal tract which can result in long−term complications. As an alternative to the use of intestinal tissue, development of a urinary diversion which regenerates non-absorptive urinary tissue mucosa from a product known as Neo−Urinary Conduit (NUC) has been developed. The NUC is produced by seeding an autologous population of adipose-sourced smooth muscle cells (SMC) onto a biodegradable PLGA scaffold. In the current study, we provide a macroscopic and histological assessment of results from animal studies showing the regenerative outcomes of the NUC and compare these results to the results from conduits explanted 7 weeks and 10 months post-implantation from two patients enrolled in a Phase 1 clinical study which demonstrated for the first time urinary tissue regenerative outcomes in humans.
Materials & Methods
SMC was isolated from fat, ex vivo expanded, and grown on a biodegradable PLGA scaffold. The porcine model involved ureteral implantation into a scaffold lined with AD−SMC. NUC wrapped with omentum or peritoneum provides blood supply for tissue regeneration. Same technique is performed in human patients after radical cystectomy. 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.
NUC implantation in pigs and humans resulted in regeneration of an incontinent urinary−tissue−lined diversion. Regenerated tissue 3 months after implantation in the porcine model demonstrated formation of urinary tissue containing all layers of genitourinary tract. Luminal surface was covered by urothelium (CK7+) and smooth muscle bundles (calponin +) were visualized and predominantly observed in the proximal and mid segments of NUC. In the phase 1 clinical trial, 7−weeks post implantation, human explant showed evidence of early stages of urinary tissue. Urothelium (CK7+) and epithelium (cytokeratin AE1/AE3) was observed throughout the NUC, followed by non−layered smooth muscle cells (calponin +) in the remaining body of the NUC. At 10−months post−implantation a mature organ composed of urinary tissue was obtained. Urothelium and tunica muscularis layer was fully developed and characterized by the presence of layered smooth muscle bundles surrounded by a fibrovascular stroma of the regenerated conduit’s wall. There was also innervation (neurofilament 160) of the NUC from the native ureters.
The findings in human explants are consistent with the translational porcine model and support the use of AD−derived SMC seeded onto a scaffold to provide an innate regenerative response. Translation of technology from a porcine model is demonstrated through native−like tissue regeneration in humans enrolled in a Phase 1 first in human clinical trial. However, the development of a clinically functional urinary conduit remains to be proven in an ongoing multi-center phase 1 clinical trial.