Mechanisms of Action of Umbilical Cord Mesenchymal Stem Cells in Type 2 Diabetes Mellitus Treatment

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease involving multiple organs. It affects the quality of life of patients significantly. Traditional treatments have certain limitations, such as side effects caused by long-term intake, complications owing to prolonged pathogenesis, and limited therapeutic effects. However, cellular therapy has demonstrated remarkable positive effects, such as improved blood glucose and lipid levels, repaired pancreatic and renal structure, and improvements in diabetic complications. We constructed a T2DM rat model in this study. Rats were divided into six groups to assess the best injection method. Four groups were further formed to evaluate the anti-inflammatory effects of umbilical cord mesenchymal stem cells (UC-MSCs). The anti-inflammatory effects of human UC-MSCs were demonstrated using inflammatory factors and M2 macrophages, a type of anti-inflammatory macrophage. Western blotting and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining were performed to further elaborate the mechanism of action of hUC-MSCs in T2DM treatment. In this study, we confirmed that hUC-MSCs could efficiently treat T2DM. We conducted an ameliorative fasting blood glucose (FBG) test and an oral glucose tolerance test (OGTT). We assessed the recovery of liver and renal function using biochemical factors (such as TC, TG, BUN, and Ccr, among others). The anti-inflammatory effect of the treatment was demonstrated by the increased expression of biomarkers in M2 macrophages and reduced secretion of inflammatory cytokines, such as TNF-a. The regulatory mechanism involved the TLR4/NF-kB signaling pathway. The apoptosis of pancreatic tissues in T2DM was also inhibited by UC-MSCs, contributing to relief from T2DM symptoms. In conclusion, our findings confirmed that efficient T2DM treatment using hUC-MSCs treating was related to anti-inflammatory effects mediated via TLR4/NF-kB signaling inhibition and apoptosis attenuation in pancreatic tissues.