Muscular tubes of urethra engineered from adipose-derived stem cells and polyglycolic acid mesh in a bioreactor.

We have explored the feasibility of using adipose-derived stem cells (ADSCs) and polyglycolic acid (PGA) for constructing muscular tubes of urethra in a bioreactor. With the induction of by 5-azacytidine, ADSCs were found to acquire a myoblast phenotype. Here we seeded ADSCs in a PGA mesh to construct the cell-PGA complex that was cultured statically for 1 week. Afterwards, the cell-PGA complex was subjected to extension stimulation in a bioreactor for 5 weeks. A muscular tube of urethra was formed after 6 weeks. Histological examination showed differentiated ADSCs and collagenous fibers had orientated well. This study demonstrates that tissue engineering of urethra tissues in vitro by using a bioreactor leads to tissue maturation and the differentiation of ADSCs. This novel technique could provide an effective approach for urethra tissue engineering.

The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen.