Urethral Reconstruction Using Mesothelial Cell-Seeded Autogenous Granulation Tissue Tube: An Experimental Study in Male Rabbits

Abstract

Objective. This study was to evaluate the utility of the compound graft for tubularized urethroplasty by seeding mesothelial cells onto autogenous granulation tissue. Methods. Silastic tubes were implanted subcutaneously in 18 male rabbits, of which nine underwent omentum biopsies simultaneously for in vitro expansion of mesothelial cells. The granulation tissue covering the tubes was harvested 2 weeks after operation. Mesothelial cells were seeded onto and cocultured with the tissue for 7 days. A pendulous urethral segment of 1.5 cm was totally excised. Urethroplasty was performed with mesothelial cell-seeded tissue tubes in an end-to-end fashion in nine rabbits and with unseeded grafts in others as controls. Serial urethrograms were performed at 1, 2, and 6 months postoperatively. Meanwhile, the neourethra was harvested and analyzed grossly and histologically. Results. Urethrograms showed cell-seeded grafts maintained wide at each time point, while strictures formation was found in unseeded grafts. Histologically, layers of urothelium surrounded by increasingly organized smooth muscles were observed in seeded grafts. In contrast, myofibroblasts accumulation and extensive scarring occurred in unseeded grafts. Conclusions. Mesothelial cell-seeded granulation tissue tube can be successfully used for tubularized urethroplasty in male rabbits.

Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction

“…Moreover, it was shown that the detected transitional epithelial cells in the treated urethral defect areas were originated from implanted epidermal cells (keratinocytes) suggesting that the urethral environment may have directed transformation of implanted keratinocytes into transitional epithelial cells [75]. Recently a similar finding in supporting the regenerative capability of cell-seeded tubularised silastic graft in treating long urethral stricture was also reported by Jiang et al [12] in 2017.…”

“…Six months post-operation, the results revealed development of continuous epithelial layer and organized smooth muscle bundles with no evidence of urethral stricture in animals receiving seeded tubularized graft as opposed to control group, which was treated, by unseeded tubularized graft. Also severe fibrosis and progressive shrinkage were only observed in unseeded grafts [12].…”

“…Progenitor cells with restricted differentiation capacity such as (i) epithelial cells including autologous urothelial cells [5], autologous epidermal cells [11], autologous mesothelial cells [12], and autologous oral keratinocytes [13] and (ii) smooth muscle cells have been used as cell sources for engineering of bladder and urethra [1,14].…”

Cells Involved in Urethral Tissue Engineering: Systematic Review

“…The urethral lumen in the control group was severely contracted, whereas in the experimental group wide urethral calibers were observed. Moreover, the newly formed urothelium replaced the mesothelium 4 weeks post-implantation 29 .…”

Outcome of urethral reconstruction among vesico-vaginal fistula patients: a cross-sectional study

“…Urethral reconstruction techniques also include the use of buccal mucosa graft; engineered tissue grafts are being investigated as novel management modalities. These include mesothelial cell-seeded autogenous granulation tissue tube and cell-based tissue engineering approach [23,24]. Ansari and Karram reported female urethral reconstruction for complete urethral loss using acellular porcine urinary bladder matrix with successful clinical outcomes [25].…”