Bioingegneria tissutale in Urologia: è possibile oggi rigenerare la vescica?
Urologia 2012; 79(4): 232 - 239
Article Type: ORIGINAL RESEARCH ARTICLE
Paolo Caione, Simona Gerocarni Nappo, Renata Boldrini, Daniela Zavaglia, Francesco Zinno, Alberto Lais
Background: Tissue engineering techniques aim to substitute or restore the structure and function of organs and systems. The bladder has been recently considered as a promising organ for tissue engineering regeneration for augmentation or substitution. We present our experience on an experimental model and a pilot clinical study. Methods: The experimental model: 10 minipigs underwent 50% volume cystectomy and bladder wall substitution using a 5 × 4 cm acellular intestinal submucosa membrane as graft, covered by omentum. In 4 pigs, autologous stem cells, bone marrow-derived, were injected into the scaffold. The animals were sacrificed at 5 weeks, and 3 months from grafting. The clinical study: 5 exstrophic patients, 8-17 years old (mean 10.4 years), presenting poor bladder capacity and compliance after bladder closure and urethra-genitalia reconstruction, who refused enterocystoplasty, received intestinal submucosa membrane (cm 5 × 4) bladder grafting. Follow-up lasted 3 years. Results: All animals but 1 survived. The regenerated bladders had normal capacity. The newly developed wall was lined by normal looking mucosa. At histology, 3 layers were well defined: urothelium (inner), fibrocells and muscular cells within rich connective tissue (intermediate) and a well vascularized adventitial coat. No residual scaffold was observed at 3 months. The muscular component was 28% in the engineered bladder wall, versus 44% in the native wall (p>0.05). In the clinical study at 6 months’ follow-up, bladder capacity increased from 102 mls to 136 mls (mean). The difference was significant (p>0.05). At biopsy, the newly generated bladder wall appeared similar to the animal model histology. No complications occurred, but 2 patients required enterocystoplasty at 3 years’ follow-up. Conclusions: Bladder regeneration is feasible by tissue engineering techniques in animal models and in humans. Functional and histological results are not as with normal bladder wall. Further improvements are necessary before any extensive clinical application.