ABSTRACT
Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa (GS) and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS (GS group, n=8) or intrahepatic via portal vein (PV group, n=5). Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation (mean survival time, 7.16±0.69 days). However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group (mean survival time, 120±28.58 days; P<0.01 vs. GS group). The results of intravenous glucose tolerance test (IVGTT) confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.
Subject(s)
Animals , Dogs , Humans , Diabetes Mellitus, Experimental , Metabolism , Pathology , Therapeutics , Gastric Mucosa , Metabolism , Transplantation , Glucose , Metabolism , Glucose Tolerance Test , Graft Survival , Insulin , Metabolism , Islets of Langerhans Transplantation , Liver , Pathology , Liver Transplantation , Transplantation, AutologousABSTRACT
Objective To investigate the mechanisms of the alleviation of islet graft earlier injury in the gastric submucosa.Methods The recipients were divided into gastric submucosa group (n =8) and hepatic portal vein group (n =8).1200IEQ SD rat islets were transplanted into diabetic SD rats induced by the administration of streptozocin (STZ).Glucose tolerance test and pathological examination were performed 14 days post transplantation.30 min after the transplantation,the C-peptide of the two groups were detected.12 h after the transplantation,IL-1β and TNF-α of the two groups were examined.Results The mean survival time (MST) of grafts in gastric submucosa group was (25.9 ± 4.1) d and (16.0 ± 0.8) d (P ＜0.01) in portal vein group.The results of glucose tolerance test and immunofluorescent staining demonstrated that grafts in gastric submucosa group survived well and got excellent function 14 days post transplantation.Compared with the gastric submucosa group,after 30 min of the transplantation,C-peptide in portal vein group was significantly higher [(1.46 ± 0.28) ng/ml.vs.(3.84 ± 0.22) ng/ml,P ＜ 0.01].Additionally,the level of IL-1β [(29 ± 1.41) pg/ml.vs.(262.26 ± 53.37) pg/ml,P ＜ 0.01] and TNF-α [(23 ± 1.41) pg/ml.vs.(138.51 ± 39.5) pg/ml,P ＜ 0.01] in portal vein group,were also significantly higher than the gastric submucosa group,after 12 h of the transplantation.Conclusion Islet transplantation in gastric submucosa prolongs islet grafts survival by avoiding or alleviating IBMIR and the injuries induced by early inflammatory mediators.