ABSTRACT
BACKGROUND: Adiponectin is the only lipid-derived cytokine that exerts a protective effect on the human body, and it also plays an important role in the development and progression of diabetes mellitus. OBJECTIVE: To explore the effect of adiponectin gene-modified human amniotic membrane mesenchymal stem cell (hAMSCs) transplantation on islet neogenesis and the relevant mechanism. METHODS: Fifteen Sprague-Dawley rats without any processing were randomly selected from 98 Sprague-Dawley rats as control group. The remaining rats were used to establish diabetic models by intraperitoneal injection of 60 mg/kg streptozotocin, and the animal model was successfully prepared in 75 rats. Then, the model rats were randomized into diabetic, hAMSCs, adiponectin-modified hAMSCs groups, followed by 3-day caudal vein injection of normal saline (20 μL), 2×106/L hAMSCs suspension (20 μL), and adiponectin-modified hAMSCs suspension (20 μL), respectively. Blood glucose and serum insulin levels of all rats were detected at 7, 14, 21, 28 days after transplantation. RT-PCR and western blot were used to test mRNA and protein expression of adiponectin, Caspase3 and Bax, respectively at 21 days after transplantation. Pathological changes of the rat pancreatic tissues were observed by hematoxylin-eosin staining. Apoptosis of islet cells was observed using TUNEL method. RESULTS AND CONCLUSION: (1) Compared with the control group, the blood glucose level was obviously increased, while the serum insulin level was significantly decreased in the diabetic group (P < 0.05). Compared with the diabetic group, the blood glucose level was obviously decreased, while the serum insulin level was significantly increased in the hAMSCs group (P < 0.05). Compared with the hAMSCs group, the blood glucose level was further decreased, while the serum insulin level was further increased in the adiponectin-modified hAMSCs group (P < 0.05). (2) The expression of adiponectin at mRNA and protein levels was significantly higher in the adiponectin-modified hAMSCs group than the other groups (P < 0.05). (3) Compared with the diabetic group, the expression of Caspase-3 and Bax at mRNA and protein levels was significantly decreased in the adiponectin-modified hAMSCs group (P < 0.01) and in the hAMSCs group (P < 0.05). (4) In the adiponectin-modified hAMSCs group, the morphology of the islet was dramatically recovered and the number of islet cells was minimally reduced. To conclude, the adiponectin-modified hAMSCs transplantation can improve the blood glucose level and promote islet neogenesis in diabetic rats, probably by regulating the expression of Caspase-3 and Bax in the islet and reducing apoptosis in islet cells.