Terminal urothelium differentiation of engineered neoureter after in vivo maturation in the "omental bioreactor"

H Baumert,G Fromont,D Mansouri,V Molinié,B Malavaud,P Simon,M Hekmati,W Massoud

doi:10.1590/s1677-55382007000600036

Abstract

Abstract Objective Long ureteric defects may theoretically be repaired with the use of tissue-engineered neoureter. However, attempts to construct such a neoureter in animal models have failed because of major inflammatory response. Avoidance of such inflammation requires a well-differentiated urothelium. We investigated whether omental maturation of a seeded construct in a pig model could achieve terminal differentiation of the urothelium to allow construction of a stricture-free neoureter. Material and method Bladder biopsies were taken to allow urothelial and smooth muscle cell cultures. These cultured cells were used to seed small intestinal submucosa (SIS) matrix. After 2 wk of cell growth, the in vitro SIS-seeded construct was shaped around a silicone drain and wrapped by the omentum to obtain neoureters. These neoureters were left in the omentum without any contact with urine, and then harvested 3 wk later for histologic and immunohistochemical studies. Results Before implantation, the in vitro constructs were composed of a mono- or bilayer of undifferentiated urothelium overlying a monolayer of smooth muscle cells. After 3 wk of omental maturation, these constructs were vascularized and comprised a terminally differentiated multilayered urothelium with umbrella cells over connective tissue and smooth muscle cells, with no evidence of fibrosis or inflammation. Conclusion We obtained, for the first time, with this model of in vivo maturation in the omentum, a mature neoureter composed of a well-differentiated multilayered urothelium.

Highlights

Terminal urothelium differentiation of engineered neoureter after in vivo maturation in the “omental bioreactor” Baumert H, Mansouri D, Fromont G, Hekmati M, Simon P, Massoud W, Molinié V, Malavaud B Department of Urology, Paris Saint Joseph Hospital Trust, Paris, France Eur Urol
We investigated whether omental maturation of a seeded construct in a pig model could achieve terminal differentiation of the urothelium to allow construction of a stricture-free neoureter
Before implantation, the in vitro constructs were composed of a mono- or bilayer of undifferentiated urothelium overlying a monolayer of smooth muscle cells

Summary

Introduction

Terminal urothelium differentiation of engineered neoureter after in vivo maturation in the “omental bioreactor” Baumert H, Mansouri D, Fromont G, Hekmati M, Simon P, Massoud W, Molinié V, Malavaud B Department of Urology, Paris Saint Joseph Hospital Trust, Paris, France Eur Urol. Attempts to construct such a neoureter in animal models have failed because of major inflammatory response. We investigated whether omental maturation of a seeded construct in a pig model could achieve terminal differentiation of the urothelium to allow construction of a stricture-free neoureter.

Results

Conclusion