Epigallocatechin-3-gallate protects Wharton's jelly derived mesenchymal stem cells against in vitro heat stress

Abstract The deteriorating effects of heat stress abrogate the therapeutic implications of human Wharton's jelly derived mesenchymal stem cells (hWJMSCs) transplanted in burn wounds. Topically applied green tea extract comprising epigallocatechin-3-gallate (EGCG) is known to repair burn wounds. Here, we investigated the protective role of EGCG priming of hWJMSCs against heat-induced stress in vitro along with the involved underlying mechanism. EGCG ameliorated heat-induced injuries as demonstrated by significantly improved cell morphology, viability, triggered cell migration and enhanced expression of heat shock proteins. In addition, decreased lactate dehydrogenase release and reduced percentage of senescent and apoptotic cells were observed. EGCG priming alleviated the detrimental effects of thermal stress in hWJMSCs as observed by significant down-regulation in expression of BCL2 associated X (BAX), interleukin 6 (IL6), and interleukin 1 beta (IL1β) genes, while proliferating cell nuclear antigen (PCNA), BCL2 like 1 (BCL2L1), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGFβ1), hepatocyte growth factor (HGF) and interleukin 4 (IL4) genes were up-regulated. Accompanying gene expression data, EGCG primed cells exposed to heat stress also exhibited remarkably increased secretion of VEGF, HGF, epidermal growth factor (EGF), stromal-derived factor 1 (SDF1) proteins while the reduced release of IL-6, and tumor necrosis factor-alpha (TNF-α) proteins. Further, synergistic activation of extracellular-signal-regulated kinase (ERK) and protein kinase B (PKB/AKT) proteins was observed. These findings suggest that EGCG priming might enhance the therapeutic efficacy of hWJMSCs in the burnt tissue through regulation of ERK and AKT signaling pathways, and improved cellular responses.