Construction of ureteral grafts by seeding bone marrow mesenchymal stem cells and smooth muscle cells into bladder acellular matrix

Abstract

Background: Congenital or acquired abnormalities may cause an ureteral injury or defect. The main methods to reconstruct a long ureter often cause serious complications. In this study, we sought to construct a tissue-engineered graft by seeding bone marrow mesenchymal stem cells (MSCs) and smooth muscle cells (SMCs) into a bladder acellular matrix (BAM) for ureteral reconstruction.

Methods: Isolated, proliferated, and in vitro identified rabbit bone marrow MSCs and SMCs were seeded into BAM as the experimental group. Grafts only seeding SMCs were the control group. Cell-seeded grafts were used to construct tissue-engineered tubular grafts (TETG) for transplantation into the rabbit's omentum for 2 weeks before ureteral reconstruction. Evolutionary histology was performed at 2, 4, 8, and 16 weeks postoperatively. Renal function and ureteral obstruction were evaluated using intravenous urography at 16 weeks.

Results: Flow cytometry demonstrated bone marrow MSCs to express CD29, CD44, CD90, but not CD34. Histological examination revealed consistent regeneration of TETG urothelium in the experimental group. At 8 and 16 weeks after TETG grafting in vivo, multilayer urothelium covered the entire lumen with visible neovascularization within the center. Organized smooth muscle bundles were observed. Intravenous urography demonstrated no ureteral stricture or hydronephrosis. The 5 rabbits were dead within 4 weeks postoperatively. Autopsy showed scar formation inside the graft with severe hydronephrosis.

Conclusion: We successfully constructed a TETG by seeding bone marrow MSCs and SMCs into BAM for ureteral reconstruction. Thus bone marrow MSCs can potentially promote urothelial regeneration to achieve a tissue-engineered ureter.