Implantation of autologous bone-marrow-derived cells reconstructs functional urethral sphincters in rabbits

The purpose of this study was to determine if implantation of autologous bone-marrow-derived cells has the potential to treat stress urinary incontinence caused by intrinsic sphincter deficiency. Bone marrow cells harvested from femurs of New Zealand White rabbits were cultured for 10 days. Seven days before implantation, the urethral sphincters located at the internal urethral orifice were cryo-injured by spraying liquid nitrogen for 15 s. The cultured autologous bone-marrow-derived cells were implanted 7 days after cryo-injury. For controls, cell-free solutions were injected. At 7 and 14 days after implantation, leak point pressures were determined and the urethral sphincters were examined by immunohistochemistry. At 7 and 14 days, the cell-implanted regions contained numerous striated and smooth muscle-like cells expressing myoglobin and smooth muscle actin, respectively. The proportions of myoglobin- and smooth muscle actin-expressing areas in both the 7- and 14-day cell-implanted regions were significantly higher than in controls. By 14 days, these differentiated cells formed contacts with similar cells, creating layered muscle structures. At that time, the leak point pressure of the cell-implanted rabbits was significantly higher than that of the controls. In conclusion, autologous bone-marrow-derived cells can reconstruct functional urethral sphincters.