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


METHODS
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.


CONCLUSIONS
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.
Baumert
Hervé
H
Department of Urology, Paris Saint Joseph Hospital Trust, Paris, France. baumertherve@yahoo.fr
Mansouri
Dhouha
D
Fromont
Gaëlle
G
Hekmati
Mehrak
M
Simon
Pascal
P
Massoud
Walid
W
Molinié
Vincent
V
Malavaud
Bernard
B
D000818:Animals; D019149:Bioreactors; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D009130:Muscle, Smooth / Q000166:cytology / Q000637:transplantation; D009852:Omentum; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014517:Ureteral Obstruction / Q000601:surgery*; D019459:Urothelium / Q000166:cytology / Q000637:transplantation*