Treatment of vesicoureteric reflux in a sheep model using subureteric injection of cultured fetal-bladder tissue

Abstract

To investigate the role of injecting cultured fetal-bladder tissue into the region of the vesicoureteric orifice (VUO) to correct surgically produced vesicoureteric reflux (VUR), 12 Coopworth ewe lambs were studied. Four weeks after incising the intravesical segment of ureter, VUR was demonstrated by micturating cystourethrography. Bladder tissue was obtained from a fetal Coopworth lamb at 10 weeks’ gestation, cultured in RPMI 1640, and injected into the region of the VUO of 1 ureter of each lamb using an open surgical approach. The lambs were killed between 1 and 6 months after the injection. Smooth-muscle cells from the cultured fetal bladder tissue were identified by the monoclonal antibodies HHF-35 for muscle alpha-actin and D33 for muscle desmin, and by electron microscopy. One lamb died of a gastrointestinal infection at 8 weeks of age. Of the remaining 11 animals, the injection of fetal-bladder tissue corrected the reflux in 7, while it was reduced in degree in 3 and persisted unchanged in 1. The reflux on the contralateral control side was also corrected in 6 ureters and improved in 2. Using histochemical techniques, grafted fetal-bladder tissue could not be differentiated from host tissue in the region of the VUO. Histopathological studies failed to show any injected tissue in distant organs. This study has shown that surgically-induced VUR in lambs was corrected or improved by the injection of cultured fetal-bladder tissue into the submucosa adjacent to the VUO.