Engineering Mouse Bladder Tissue Grafts Using Cells Differentiated From Bone Marrow Mesenchymal Stem Cells

Background: Studies have shown that bone marrow mesenchymal stem cells (MSCs) can be induced to differentiate into urinary epithelial cells. The differentiated epithelial cells have been implanted into animals, but the use of the differentiated cells in tissue engineering has not been carried out. Objective: Epithelial cells were generated from mouse bone marrow MSCs through a cocktail of induction agents. In combination with a mouse extracellular matrix, the MSC-derived epithelial cells were taken as graft sources and used to construct tissue-engineered grafts. Methods: Bone marrow MSCs were isolated from 8-week old male mice using density gradient centrifugation. The MSCs were differentiated into epithelial cells in a conditioned medium for two weeks. Subsequently, the differentiated cells were identified and planted in the extracellular matrix to construct tissue-engineered grafts to repair the bladders. In a control group, urinary epithelial cells isolated from mice were treated with the extracellular matrix to repair the bladders. Results: MSCs were successfully cultured and amplified in vitro. The expression of the stem cell marker CD44 was reduced after its induction with the conditioned medium and the expression of the differentiated epithelial marker UP1a was increased, but not in the bone marrow MSCs. The tissue-engineered grafts constructed with differentiated cells formed stable and continuous epithelia two weeks after being transplanted into bladders, and the thicknesses of the cortexes were similar to those of the tissue-engineered grafts. Conclusion: Bone marrow MSCs can be differentiated into epithelial cells and serve as a new alternative to urothelial cells in urinary tissue engineering.