Infusion of mesenchymal stem cells culture supernatant ameliorates hyperglycemia disorders in STZ-induced diabetes mellitus rats / 解放军医学杂志

ABSTRACT

Objective To evaluate the therapeutic effect of systemic infusion of MSC culture supernatant in STZ-induced diabetic rats, and explore the mechanism of effect of MSC secretion on promoting regeneration of the islet tissues. Methods The diabetic animal model was reproduced in 35 SD rats by intraperitoneal injection of a single large dose of streptozotocin (STZ, 65mg/ kg). The 30 successfully induced diabetic rats were randomly divided into MSC culture supernatant infusion group (CM, n=15) and medium infusion group (M, n=15), and in addition, 15 normal rats were used as control. Animals were intravenously transfused with MSC supernatant (CM group) or raw medium (M group), then the contents of blood glucose were determined 3 days after infusion. The serum insulin and C-peptide levels were monitored and the intraperitoneal glucose tolerance test (IPGTT) was performed on the 7th day of infusion to evaluate the therapeutic effect of MSCs supernatant infusion in diabetic rats. Finally, all the experimental animals were sacrificed at indicated time points and the pancreatic tissues were collected for multiple immunofluorescence staining (MIFS), in order to observe the β-cell regeneration after MSCs supernatant infusion, and to further explore the possible mechanism involved in the experiment. Results At the early stage after infusion (<7 days), the blood glucose level declined and the contents of serum insulin and C-peptide increased obviously in CM group as compared with that of M group (P<0.05). IPGTT showed that the islet function was significantly enhanced in CM group compared with M group. MIFS showed that the number of β cells in the destroyed islets in CM group rats was significantly increased as compared with that of M group rats. In addition, the proliferation rate of β cells was obviously higher in CM group (4%) than in control group (0.5%, P<0.01). Conclusion Treatment with MSCs culture supernatant obviously prompted β cell proliferation in the destroyed islets, resulting in regeneration of the islets with islet function recovery, thus it effectively controls the advance of diabetes.