Autologous myoblast transplantation in an animal model applicable as a potential bulking agent at the ureterovesical junction?

Abstract

Purpose Myoblast transplantation has been shown to augment damaged tissue. Moreover it could be used as an autologous bulking agent in refluxing vesicoureteral junctions in order to restore the damaged muscular integrity. But graft viability and the behaviour of the donor myoblasts at the ureterovesical junction have not been demonstrated yet. Material and methods Muscle biopsies from the back muscles of 5 pigs were obtained. Quality of the cells was evaluated by electrophysiological and immunohistochemical tests. Additionally they were labelled with a PKH fluorescent membrane dye to provide fluorescent marking of live cells. 5 weeks after muscle biopsies all animals underwent cell transplantation with 300 × 106 cells suspended in transplantation medium loaded into five 1-cc tuberculin syringes and injected into the ureterovesical junction. Animals were sacrificed 8 weeks later, the donor cells were identified using PKH26 labelling and fluorescence-activated cell-sorter analysis. Moreover histopathology and evaluation concerning tissue reaction at the donor site was also carried out. Results 2-3 intact autologous skeletal myoblast–derived skeletal muscle cells/visual field were found in all injected animals. However, immunohistochemistry demonstrated viability of transplanted myoblasts only at the borders of the bulking area wheras central widespread necrosis with red fluorescent cell detritus could be observed. We did not observe marked signs of an inflammatory response, even though a fibrotic scar was found at the site of injection. Conclusions These results highlight the inability of the vast majority of transplanted myoblasts to survive. Only a small portion of the cells survive when transplanted into a well vascularized area which is in favour of the assumption of an indirect impairment such as paracrine effects. Failure of myoblast transplantation in this animal study does not prove that the procedure itself is ineffective, but these results do caution against the application of in vivo myoblasts as a bulking agent.