Rosmarinic Acid Protects Adipose Tissue-Derived Mesenchymal Stem Cells in Nutrient-Deficient Conditions

One of the major challenges for stem cell therapy of ischemic organs is that the transplanted cells are confronted with nutrient deficiency and oxidative stress. Previous studies have indicated that pretreatment of stem cells with cytoprotective phytochemicals improves their therapeutic potential. This study was aimed to investigate whether rosmarinic acid can enhance survival of adipose tissue-derived stem cells (ASCs) in nutrient-deficient culture as an in vitro model of ischemia. The ASCs were isolated from subcutaneous adipose tissue of male adult Wistar rats and incubated for 24 h with rosmarinic acid in nutrient-deficient (glucose- and serum-deprived, GSD) culture medium. In a separate experiment, ASCs were pre-incubated for 4 h with rosmarinic acid and then exposed to GSD conditions for 24 h. The viability of ASCs was determined using thiazolyl blue tetrazolium bromide assays. The effect of rosmarinic acid on the cell cycle was evaluated using propidium iodide staining. GSD conditions significantly decreased the viability of ASCs and enhanced the generation of reactive oxygen species (ROS), lipid peroxidation, sub-G1 cell populations, and necrosis. Both pre-incubation and incubation of ASCs with 0.75~6 μM rosmarinic acid significantly increased cell viability in GSD conditions. Rosmarinic acid further decreased the level of ROS, lipid peroxidation, the percent of cells in sub-G1 stage, and necrosis in GSD conditions. These findings suggest that rosmarinic acid enhances survival of ASCs cultured in nutrient-deficient conditions through promoting antioxidant effects. Therefore, rosmarinic acid may help preserve ASCs survival after they are transplanted into ischemic organs.