Protective Role of Stem Cell Derived Extracellular Vesicles in an In VitroModel of Hyperglycemia-Induced Endothelial Injury

Background: Adipose and bone marrow derived mesenchymal stem cells are two populations of multipotent adult stem cells with immunosuppressive, anti-inflammatory, and regenerative properties. It has been previously described that extracellular vesicles (EVs) derived from stem cells possess pro-regenerative and pro-angiogenic abilities. Hyperglycemia is a pathological condition affecting diabetic patients. Long term effects of hyperglycemia are endothelial dysfunction and vascular lesions leading to diabetic microangiopathy. The aim of the present study was to evaluate whether stem cell-derived EVs may inhibit endothelial cells dysfunction induced by hyperglycemia to mimic human microangiopathy. Methods: We set up an in vitro hyperglycemic model by culturing human microvascular endothelial cells in hyperglycemic constant or intermittent conditions for 7 days, in order to mimic a chronic damage. At day 5, endothelial cells were incubated with adipose and mesenchymal stem cell-derived EVs or vehicle alone for 48 hr. At day 7, we evaluated apoptosis, oxidative stress, and capillary-like formation ability on Matrigel. Results: Intermittent and constant high glucose models significantly decreased endothelial cell proliferation, increased number of apoptotic cells, promoted oxidation of intercellular proteins, and reduced capillary-like structure formation. Treatment with both kinds of EVs significantly restored proliferation, inhibited apoptosis and oxidation, and restored capillary-like formation. Conclusions: The results of the present study demonstrate that adipose and bone marrow mesenchymal stem cell-derived EVs may inhibit the endothelial dysfunction induced by high glucose concentration, which mimic diabetic microvascular injury.