Dissecting the effects of preconditioning with inflammatory cytokines and hypoxia on the angiogenic potential of mesenchymal stromal cell (MSC)-derived soluble proteins and extracellular vesicles (EVs)

Mesenchymal stromal cells (MSCs) are characterized by a regulatory phenotype and respond promptly to the environmental signals modulating their secretory activity. An appropriate preconditioning may induce MSCs release secretomes with an enhanced regenerative potential. However, it fails take into account that composed both soluble factors extracellular vesicles (EVs), whose functions could be altered differently approach. Here we demonstrate MSC secretome is strongly modulated simultaneous stimulation hypoxia pro-inflammatory cytokines, used mimic harsh environment present at site of injury. We observed variations influenced angiogenic potential different fractions. Upon inflammation, pro-angiogenic capacity component was inhibited, regardless oxygen level, while EV-encapsulated not significantly affected inflammatory stimuli. These effects were accompanied modulation secreted proteins. On one hand, inflammation-activated proteins mainly involved in interaction innate immune tissue remodeling/repair; on other when exposed inflamed environment, they levels expression process. The cargo content (in terms miRNAs) corresponding EV fractions less sensitive influence external Our findings suggest therapeutic efficacy MSC-based therapies selecting approach carefully discriminating its components.