Epigallocatechin-3-gallate maintains Th1/Th2 response balance and mitigates type-1 autoimmune diabetes induced by streptozotocin through promoting the effect of bone-marrow-derived mesenchymal stem cells.

ABSTRACT

Stem-cell-based therapy is one of the most promising therapeutic strategies owing to its regenerative and immunomodulatory properties. Epigallocatechin-3-gallate (EGCG), a known antioxidant and anti-inflammatory agent, has beneficial effects on cellular protection. We aimed to elucidate the feasibility of using EGCG, along with bone marrow-derived mesenchymal stem cells (BM-MSCs), to improve pancreatic damage through their immune regulatory functions in an experimental model of type 1 diabetes mellitus (T1DM) induced by multiple injections of streptozotocin (STZ). BM-MSCs were isolated from C57BL/6 mice and characterized. The diabetic groups were treated intraperitoneally with PBS, MSCs, EGCG, and a combination of MSCs and EGCG. Real-time PCR assays showed that MSCs with EGCG modulated T-bet and GATA-3 expression and upregulated the mRNA levels of Foxp-3 more efficiently. Analyses of spleen-isolated lymphocytes revealed that combinational treatment pronouncedly increased regulatory cytokines and decreased pro-inflammatory cytokines and splenocyte proliferation. The histopathological assessment demonstrated that co-treatment significantly reduced insulitis and recovered pancreatic islet morphology. Furthermore, the combination of MSCs and EGCG is associated with downregulated blood glucose and enhanced insulin levels. Therefore, combined therapy with EGCG and MSCs holds clinical potential for treating T1DM through synergetic effects in maintaining the Th1/Th2 response balance and promoting the regeneration of damaged pancreatic tissues.