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| In vitro-derived insulin-producing cells modulate Th1 immune responses and induce IL-10 in streptozotocin-induced mouse model of pancreatic insulitis |
| Gholamreza Daryabor a , Esmaeil Hashemi Shiri a , Zahra Amirghofran a , b , Eskandar Kamali-Sarvestani a , b , ∗ |
a Autoimmune Diseases Research Center, Medical School, Shiraz University of Medical Sciences, Shiraz 71345-1798, Iran
b Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz 71345-1798, Iran
∗ Corresponding author at: Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz 71345-1798, Iran.
E-mail address: immunol2@gmail.com (E. Kamali-Sarvestani). |
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Abstract Background: Insulitis is defined by the presence of immune cells infiltrating in the pancreatic islets that might progress into the complete β-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 consecuti ve 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 IPC-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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2021, Vol. 20 
