In vitro-derived insulin-producing cells modulate Th1 immune responses and induce IL-10 in streptozotocin-induced mouse model of pancreatic insulitis
摘要Background:Insulitis is defined by the presence of immune cells infiltrating in the pancreatic islets that might progress into the completeβ-cell loss.The immunomodulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have attracted much attention.This study aimed to evaluate the possible immunomodulatory effects of rat BM-MSCs and MSCs-derived insulin-producing cells (IPCs) in a mouse model of pancreatic insulitis.Methods:Insulitis was induced in BALB/c mice using five consecutive doses of streptozotocin.MSCs or IPCs were directly injected into the pancreas of mice and their effects on the expression of Th subsets-related genes were evaluated.Results:Both BM-MSCs and IPCs significantly reduced the expression of pancreatic Th1-related IFN-γ(P < 0.001 and P < 0.05,respectively) and T-bet genes (both P < 0.001).Moreover,the expression of IL-10 gene was significantly increased in lPC-treated compared to BM-MSC-or PBS-treated mice (P < 0.001 both comparisons).Conclusions:BM-MSCs and IPCs could successfully suppress pathologic Th1 immune responses in the mouse model of insulitis.However,the marked increase in IL-10 gene expression by IPCs compared to BM-MSCs suggests that their simultaneous use at the initial phase of autoimmune diabetes might be a better option to reduce inflammation but these results need to be verified by further experiments.
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