ROS-mediated regulation of MSC angiogenic activity

Mesenchymal stromal cells(MSCs) are promising candidates for cell therapy. However, little is known about regulatory role of ROS in MSCs. In present study we evaluated effects of intracellular ROS on angiogenic activity of MSCs cultured under different oxygen conditions and during long‑term in vitro culture. MSCs were isolated from human adipose tissue and maintained in standard or hypoxic oxygen conditions. Senescence was induced by long-term culture of MSCs till 20th passage. ROS was induced by photodynamic treatment(PDT). We demonstrated that senescence as well as acute hypoxia was accompanied by 2-3-fold increase of intracellular ROS level. No significant changes were found between MSCs cultured under 20% and 5%O2. Long-term culture of MSCs didn’t affect IL-8 and VEGF production while low-fluence PDT resulted in significant increase in IL-8 and VEGF, but not TGF secretion. The PDT effect was less pronounced under acute hypoxia. Then we evaluated the effects of ROS on MSC angiogenic activity using chorioallantoic membrane assay. MSC senescence and acute hypoxia impaired MSC angiogenic activity while PDT promoted angiogenesis via stimulation of tubule complexes and vessels formation. Thus, ROS regulate angiogenic activity of MSCs. However, effects of ROS on MSC activity strongly depend on MSC state.