Effect and mechanisms of human Wharton's jelly-derived mesenchymal stem cells on type 1 diabetes in NOD model

Type 1 diabetes is an autoimmune disease that results from an inflammatory destruction of beta-cells in islets. Mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) own a peculiar immunomodulatory feature and might reverse the inflammatory destruction and repair the function of beta-cells. Sixty NOD mice were divided into four groups, including normal control group, WJ-MSCs prevention group (before onset), WJ-MSCs treatment group (after onset), and diabetic control group. After homologous therapy, onset time of diabetes, levels of fasting plasma glucose (FPG), fed blood glucose and C-peptide, regulation of cytokines, and islet cells were examined and evaluated. After WJ-MSCs infusion, FPG and fed blood glucose in WJ-MSCs treatment group decreased to normal level in 6-8 days and maintained for 6 weeks. Level of fasting C-peptide of these mice was higher compared to diabetic control mice (P = 0.027). In WJ-MSCs prevention group, WJ-MSCs played a protective role for 8-week delayed onset of diabetes, and fasting C-peptide in this group was higher compared to the other two diabetic groups (P = 0.013, 0.035). Compared with diabetic control group, frequencies of CD4(+)CD25(+)Foxp3(+) Tregs in WJ-MSCs prevention group and treatment group were higher, while levels of IL-2, IFN-gamma, and TNF-alpha were lower (P < 0.001); the degree of insulitis was also depressed, especially for WJ-MSCs prevention group(P < 0.05). Infusion of WJ-MSCs could aid in T1DM through regulation of the autoimmunity and recovery of islet beta-cells no matter before or after onset of T1DM. WJ-MSCs might be an effective method for T1DM.