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

• Published in: Endocrine Vol. 48; no. 1; pp. 124 - 134
• Main Authors: Hu, Jianxia, Wang, Yangang, Wang, Fang, Wang, Luan, Yu, Xiaolong, Sun, Ruixia, Wang, Zhongchao, Wang, Li, Gao, Hong, Fu, Zhengju, Zhao, Wenjuan, Yan, Shengli
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2015
• Subjects: Animals; Blood Glucose - metabolism; C-Peptide - metabolism; Cell Differentiation; Cytokines - blood; Diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - prevention & control; Endocrinology; Female; Humanities and Social Sciences; Internal Medicine; Islets of Langerhans - metabolism; Lymphocyte Count; Medicine; Medicine & Public Health; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - physiology; Mice; Mice, Inbred NOD; multidisciplinary; Original Article; Science; Spleen - cytology; Wharton Jelly - cytology; T cells; Type 1 diabetes; Immunomodulation; Islet β-cells; Mesenchymal stem cells
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-014-0219-9

Type 1 diabetes is an autoimmune disease that results from an inflammatory destruction of β-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 β-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-γ, and TNF-α 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 β-cells no matter before or after onset of T1DM. WJ-MSCs might be an effective method for T1DM.