A tissue-engineered conduit for urinary diversion using bone marrow mesenchymal stem cells and bladder acellular matrix

Abstract

Ileal conduits are commonly used in bladder cancer treatment and in pediatric patients who require urinary diversion surgeries. We constructed a tissue-engineered conduit using bone marrow mesenchymal stem cells (BMSCs) and a bladder acellular matrix (BAM) and transplanted it into rabbits for urinary diversion to evaluate the feasibility of its clinical application. Rabbit BMSCs were isolated, expanded in vitro, and were then treated with a conditional medium for 3 weeks, allowing the BMSCs to transform into urothelium-like cells. These cells were seeded onto BAM and cultured for another week. The cell-matrix grafts were then sewn into a conduit approximately 4 cm in length and 1 cm in diameter and were implanted as conduits for urinary diversion in 12 male rabbits. Rabbits were sacrificed at 1, 2, and 4 week after operation. Histologic examinations were performed using hematoxylin and eosin staining and tissue structures were evaluated by using immunohistochemistry. BMSCs can transform into urothelium-like cells that express the urothelium-specific proteins uroplakin 1A (UPK1A), cytokeratin 7 (CK7), and cytokeratin 13 (CK13). These cells are able to generate epithelial coverage in the conduit lumen based on BAM. Immunohistochemistry showed positive staining with AE1/AE3, UPK1A, and tight junction protein 1 (ZO-1), indicating the presence of mature and functional epithelial cells on the lumen of the conduit. BMSCs may represent a new source cell for urinary tissue engineering, and it is feasible to construct a conduit with transformed BMSCs and BAM for urinary diversion in rabbits.