Transplantation of human stem cells from the apical papilla for treating dextran sulfate sodium-induced experimental colitis / 中国组织工程研究

ABSTRACT

BACKGROUND: Stem cells from the apical papilla (SCAP) play important roles in the formation and development of dental roots. However, the immune-modulating capacity of SCAP has not been fully elucidated. OBJECTIVE: To test the therapeutic effects of transplantation of SCAP on dextran sulfate sodium-induced experimental colitis. METHODS: Twenty-four C57/BL6 mice were equally divided into four groups (normal control, positive control, SCAP treatment group, and FasL-knockdown SCAP group), and latter three groups of mice were induced to acute experimental colitis by 3% dextran sulfate sodium in drinking water. At day 3 after modeling, model mice were treated with PBS, human SCAP (2×106 cells), and FasL-knockdown SCAP via intraperitoneal injection, respectively. Inflammation was evaluated by measuring body mass and length of the colon, detecting levels of interleukin 1β, interleukin 6 and tumor necrosis factor α, as well as histological analyses at day 10 after modeling. Levels of Tregs in mesenteric lymph nodes in mice were detected using flow cytometric analysis. RESULTS AND CONCLUSION: SCAP transplantation could ameliorate the inflammation in dextran sulfate sodium-induced colitis mice, and body mass loss and symptoms were significantly improved. Pathological score and the levels of three inflammatory cytokines in the colon tissue decreased significantly. Flow cytometric analysis revealed an increased level of Tregs in mesenteric lymph nodes. Knocking down of FasL gene in SCAP abrogated the therapeutic effects of SCAP in ameliorating dextran sulphate sodium-induced colitis. Therefore, Fas-FasL pathway played an important role in the underlying mechanism of the immune-modulating capacity of SCAP.