PD8-08 A PORCINE MODEL OF TOTAL CYSTECTOMY AND URINARY REPLACEMENT BY TISSUE ENGINEERED URINARY DIVERSION USING A BIODEGRADABLE TUBULAR SCAFFOLD SEEDED WITH AUTOLOGOUS SMOOTH MUSCLE CELLS

INTRODUCTION AND OBJECTIVES: The present study was performed to investigate human mesenchymal stem cells (B10) directly transplanted to the bladder wall are capable of inhibiting collagen deposition and improve cystometric parameters in SCI rats. METHODS: B10 were labeled with fluorescent silica magnetic nanoparticles (MNP) contained rhodamine B isothiocyanate (RITC) conjugated to terminal silanol groups.. Forty 6-week old female Sprague-Dawley rats were divided into 4 groups (group 1: control, group 2: sham operation, group 3: SCI, group 4: SCI rats receiving B10). For SCI model, contusion was performed on the thoracic spinal cord very severe intensity weight drop. Four weeks after the onset of SCI, B10 were injected into the bladder wall. Serial T2-weighted MR images were taken immediately B10 injection (1�106 cells) and at 4 weeks post-transplantation. Locomotor behavioral tests were performed using rotarod, BassoeBeattieeBresnahan (BBB) test and voiding response was assessed at 4 weeks after transplantation and bladder was harvested. Nissl staining of spinal cord sections was performed. RESULTS: The hindlimbs of all the animals with SCI were completely paralyzed one day after contusion injury. Both of rotarod and BBB score were 0 and the development of SCI was confirmed and still preserved until 8 weeks after SCI. MR imaging of MNP-labeled B10 cells in the bladder showed hypointense signal intensities on T2weighted images until 4 weeks post-transplantation. B10 cells positive for human mitochondria antigen were found in the transplantation site indicating that MNP-labeled B10 cells survived in the bladder at 4 weeks after transplantation. Transplanted B10 differrentiated to smooth muscle cells. The SCI group showed a higher collagen deposition than the sham operation group (P<0.05). The group with transplantation of B10 hMSCs after SCI showed a lower collagen deposition than the group with SCI (P<0.05, Fig. 7). Intercontraction interval decreased after SCI but it recovered after B10 treatment. Maximal voiding pressure and residual urine volume increased after SCI but it recovered after B10 treatment. MNP-B10 transplanted into rat bladder survived 4 weeks post-transplantation using antihuman nuclear antibody staining and MR imaging. CONCLUSIONS: Transplanted B10 directly transplanted to the bladder wall inhibited the bladder fibrosis and mediated recovery of bladder dysfunction in the rat SCI model. Transplantation of mesenchymal stem cells could be a novel therapeutic strategy against bladder dysfunction in patients with SCI.