Impact of combined therapy of mesenchymal stem cells and sitagliptin on a metabolic syndrome rat model.

Emerging evidence suggests that mesenchymal stem cells (MSCs) have many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of many diseases including metabolic syndrome (MetS). However, a major difficulty with stem cell therapy is to maintain cell viability, properties and function after implantation in vivo. This study aims to test the hypothesis that the combined therapy of MSCs and sitagliptin can effectively ameliorate MetS complications induced by high-fat and high-fructose diet (HFFD) in rats. Rats were fed either standard diet (Control group) or HFFD. After 3 months, a group of HFFD animals was injected by a single dose of MSCs, another group received a daily oral dose of 10 mg/kg b.w. of sitagliptin, and the third group received the combined therapy of MSCs + sitagliptin for 1 month. Both MSCs and sitagliptin restored insulin sensitivity and reduced the HOMA-IR value in HFFD rats. The hepatic IRS-1 and Akt at both gene and protein levels, as well as the hepatic protein levels of IR and GLUT4 were improved. Downregulation of CHOP and NF-κB and upregulation of hepatic HO-1 expression and activity were also reported. Although MSCs and sitagliptin as monotherapy lead to remarkable effects, the dual application revealed the best results. Interestingly, histological findings confirmed these protective effects of the combined therapy against MetS complications. Combined therapy of MSCs and sitagliptin can efficiently ameliorate the insulin resistance and promote the regeneration of hepatocytes in the metabolic syndrome rat model.