URETERAL REGENERATION: DEVELOPMENT AND HOST INTEGRATION OF A URETERAL GRAFT FROM PORCINE TISSUE

FRAUNHOFFER NICOLAS A.; ABUELAFIA, ANALIA MEILERMAN; NAZARENO, DUARTE; PACKER GHUILLERME; PICZMAN, ANDRES; LANGE, FERNANDO; CHULUYAN, EDUARDO HECTOR; FERRARIS, SERGIO; FERRARIS, SERGIO; BARRIOS, MARCELA

Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2017

Sociedad Argentina de Investigación Clínica

Ureteral injuries account for about 3% of urogenital traumas. Decellularized tissues have emerged as an alternative to ureteral repair but the available protocols have failed in functional host integration. The aim of this study was to develop and validate in vivo a ureteral graft from porcine ureteric scaffold, seeded with adipose mesenchymal stem cells (aMSCs). 4 ureteral samples from healthy pigs were used. Tissues were decellularized using Triton X-100 1% and SDS 0.1% under intraluminal continuous perfusion in a bioreactor designed by our group. Recellularization was performed with aMSCs extracted from sheep adipose tissue. Decellularization and structural integrity were characterized by histological analysis, β-actin western blot, residual DNA content and scanning electron microscopy. Extracellular matrix (EMC) proteins and VEGF were studied by immunohistochemistry. Recellularization was evaluated by histological analysis. In addition, 41 growth factors were analyzed by protein array. The ureteral graft was implanted into the native ureter of the aMSCs donor sheep by 10 weeks, evaluating the functionality by ureterography. The implant was extracted and the tissue integration was evaluated by histological analysis. Decellularized grafts showed high structural integrity and low DNA and β-actin levels. EMC proteins and VEGF were observed. After cellularization with aMSC, the grafts analysis showed the presence of groups of aMSCs and 32 growth factors were detected. Sheep implants were functional, showing peristaltic movement and regeneration of all ureteral tissue components. These results indicate that the protocol used is successful to achieve a decellularized ureter with an intact native architecture and recellularization with aMSCs. In addition, this porcine ureteral scaffold seeded with aMSCs showed a high functional integration with the host tissue. Therefore, this type of graft may be a suitable alternative to ureteral regeneration.