Is There a Need for Smooth Muscle Cell Transplantation in Urethral Reconstruction?

Abstract

Hypospadias and urethral strictures are conditions requiring additional tissue for reconstruction. Due to a limited source of tissue, autologous skin and oral mucosa are frequently used. However, long-term follow-up studies demonstrated significant complications and diminished quality of life. Recently, a variety of tubular biodegradable biomaterials have been used. Cell seeding seems to be important to improve the host acceptance and neovascularization. To compare in vivo performance of smooth muscle cell (SMC)-seeded and unseeded tubular collagen-based scaffolds in a rabbit urethral reconstruction model. Sixteen New Zealand rabbits underwent an open-bladder biopsy for SMC harvesting. The SMCs were cultured for 3 weeks and labeled with ethynyldeoxyuridine (EdU). A 1-cm-length tubular collagen-based 0.5 wt% scaffold was seeded and cultured with SMCs and implantation in a rabbit model. Eight rabbits received SMC-seeded scaffolds for a 1-cm-length circumferential urethral repair, situated 1.5 cm from the meatus. After 1 and 3 months, four rabbits underwent a urethrography and were sacrificed. The penises underwent hematoxylin and eosin, immunohistochemistry, and EdU fluorescence staining. In the control group eight rabbits received acellular scaffolds. The SMC-seeded group presented one stricture at 1 month and one fistula at 3 months. Three strictures were present in the unseeded group at 1 month and one at 3 months. In the seeded group, more SMC expression and neovascularization was observed, and less mononuclear and giant cells could be found. All scaffolds showed luminal urothelial cell revetment. The detection of EdU-labeled SMCs revealed SMC transplantation survival. SMC-seeded tubular collagen scaffolds improved urethral regeneration in this rabbit model. Such constructs may be valuable for repair of severe urethral diseases.