Preliminary study on the establishment of neonatal pig models of islet transplantation under the renal capsule / 器官移植

ABSTRACT

Objective To explore the feasibility and potential application value of establishing the neonatal pig models of islet transplantation under the renal capsule. Methods Nine wild-type neonatal Duroc pigs were selected, including 1 animal as the control (p6307), 6 as islet transplant donors and 2 as islet transplant recipients (p6210, p6207). After islet isolation and differentiation in vitro, islet transplantation under the renal capsule of the pig was performed. Immunosuppressive therapy of tacrolimus (Tac) combined with sirolimus was given after operation. Postoperative body weight, blood glucose and serum creatinine levels of the recipients were monitored. The p6210 recipient neonatal pig was sacrificed at postoperative 4 weeks, while the p6207 recipient and the control neonatal pig were sacrificed at postoperative 8 weeks. The islet grafts under the renal capsule were collected for pathological staining and insulin immunofluorescent staining. Results After islet transplantation under the renal capsule of the pigs, the growth rate of body weight of the recipients was significantly slower than that of the control neonatal pig, accompanied with intermittent symptoms, such as anorexia and diarrhea, etc. However, the blood glucose and serum creatinine levels of the recipients did not significantly differ from preoperative levels and those of the control neonatal pig. Evident islet mass was observed under the renal capsule of the p6210 recipient. Pathological staining and insulin immunofluorescent staining confirmed that the islet mass had the function of secreting insulin, whereas no obvious islet mass could be seen under the renal capsule of the p6207 recipient. Pathological staining detected no evident islet mass, suggesting the possibility of islet transplantation failure caused by rejection in the p6207 recipient. Conclusions The establishment of neonatal pig models of islet transplantation under the renal capsule is a feasible technique, which provides preliminary evidence for the establishment of composite islet-kidney donor graft in pig models for xenotransplantation in the treatment of end-stage diabetic nephropathy.