Therapeutic effect of rosiglitazone combined with adipose-derived stem cell transplantation in rats with type 2 diabetes mellitus / 中国组织工程研究

ABSTRACT

BACKGROUND: Studies have shown that high glucose environment has a significant inhibitory effect on the survival of adipose-derived stem cells, which significantly affects the therapeutic efficacy of adipose-derived stem cells on type 2 diabetes mellitus. OBJECTIVE: To investigate the therapeutic effect of rosiglitazone combined with adipose-derived stem cell transplantation in rats with type 2 diabetes mellitus. METHODS: A total of 108 male Sprague-Dawley rats were chosen, 20 of which were randomly taken as normal controls and the rest 88 rats were used to make type 2 diabetes mellitus models through intraperitoneal injection of low-dose streptozotocin combined with high-sugar/high-fat diet. At 20 days after modeling, the model rats were randomized into model, rosiglitazone, cell transplantation and combined groups, followed by administration of normal saline (by gavage and via tail vein), rosiglitazone (by gavage), adipose-derived stem cells (via tail vein), and rosiglitazone (by gavage)+adipose-derived stem cells (via tail vein), once a day, for consecutive 7 days. Three weeks after treatment, fasting blood glucose level, insulin level, C-peptide level, body mass changes were detected; distribution and survival of adipose-derived stem cells were observed; the changes of pancreas histomorphology was observed, the apoptosis in islet cells was detected, and the CXCL1, CXCL2 and CXCR2 protein expression levels in the pancreas tissue were determined. RESULTS AND CONCLUSION: Compared with the normal control group, the fasting blood glucose level was increased (P < 0.05), while the insulin level, C-peptide level and body mass were significantly decreased in the model group (P < 0.05); the number of apoptotic islet cells was increased (P < 0.05); the expression levels of CXCL1, CXCL2 and CXCR2 in the pancreas tissue were elevated (P < 0.05); and the pancreas tissue morphologies were in disorder, with few islet cell masses. Compared with the model group, the fasting blood glucose level was decreased (P < 0.05), while the insulin level, C-peptide level and body mass were significantly increased in the rosiglitazone, cell transplantation and combined groups (P < 0.05); the number of apoptotic islet cells was decreased (P < 0.05); the expression levels of CXCL1, CXCL2 and CXCR2 in the pancreas tissue were declined (P < 0.05); and the pancreas tissue morphologies were improved to different extents, and the combined group showed the best improvement. There were many transplanted adipose-derived stem cells in the cell transplantation and combined groups, especially in the latter one. Overall findings indicate that rosiglitazone combined with adipose-derived stem cell transplantation is an effective treatment for type 2 diabetes mellitus in rats, which is better to inhibit inflammations.