Activated Endothelium Changes The Activity Of Multipotent Mesenchymal Stromal Cells During Physiological Hypoxia Or Short Hypoxic Stress In Vitro

Multipotent mesenchymal stromal cells (MSCs) are used for supplemental therapy of ischemic and inflammatory diseases. After systemic administration, transmigration of MSCs to the target tissue is accompanied by interaction with activated endothelial cells (ECs) at the site of injury. In this study, we investigated the influence of TNF-α-activated ECs on the functions of MSCs under different levels of hypoxia. For this purpose, MSCs and TNF-α activated ECs were cocultured in a direct cell-to-cell setting for a short period of time. MSCs retained their stromal phenotype and multilineage differentiation potential after interaction with activated ECs. At the same time, changes in molecules involved in MSC-cell and MSC-extracellular matrix interaction were detected. The paracrine activity of MSCs and activated ECs after interaction was demonstrated by both upregulated transcription and increased levels of pleiotropic IL-6 and IL-8. Proteases/antiproteases profiles were also altered after interaction. These data suggest that short-term interaction of MSCs with activated ECs may play an important role in tissue repair and remodeling processes. In particular, it may promote the migratory phenotype of MSCs. In comparison to physiological hypoxia – 5% O2, acute hypoxic stress (0.1% O2, 24 h) attenuated the stimulatory effects of ECs on MSCs.