Abstract
Mesenchymal stromal cells (MSCs) are considered a valuable tool for cell therapy. After systemic administration, the outcome of MSCs and endothelial cells (ECs) interactions strongly depend on the local microenvironment and tissue O2 levels in particular. In vitro analysis of EC effects on MSC regenerative potential in co-culture was performed after short-term interaction at “physiological” hypoxia (5% O2) and acute hypoxic stress (0.1% O2). At 5% O2, MSCs retained stromal phenotype and CFU-f numbers, osteogenic RUNX2 was upregulated. A shift in the expression of adhesion molecules, and an increase in transcription/synthesis of IL-6, IL-8 contributed to facilitation of directed migration of MSCs. In the presence of MSCs, manifestations of oxidative stress in ECs were attenuated, and a decrease in adhesion of PBMCs to TNF-α-activated ECs was observed. Under 0.1% O2, reciprocal effects of ECs and MSCs were similar to those at 5% O2. Meanwhile, upregulation of RUNX2 was canceled, IL-6 decreased, and IL-8 significantly increased. “Protective” effects of MSCs on TNF-α-ECs were less pronounced, manifested as NOS3 downregulation and intracellular NO elevation. Therefore, interaction with ECs at “physiological” hypoxia enhanced pro-regenerative capacities of MSCs including migration and anti-inflammatory modulation of ECs. Under acute hypoxic stress, the stimulating effects of ECs on MSCs and the “protective” potential of MSCs towards TNF-α-ECs were attenuated.
Highlights
Multipotent mesenchymal stromal cells (MSCs) are localized in a number of tissues and can be isolated and cultured in vitro
Adipose tissue-derived MSCs used in the experiments met the minimal criteria of the International Society for Cellular Therapy: they rapidly attached to plastic, had a fibroblast-like shape, and proliferated for a long time in the culture, differentiated into adipo- and osteo-directions, expressed stromal markers CD90, CD73, and CD105 and did not bear hematopoietic pan-leukocyte CD45 antigen (Figure 2a)
The aim of this study was to determine how the functional activity of MSCs changes after a short-term interaction with endothelial cells (ECs) under “physiological” hypoxia
Summary
Multipotent mesenchymal stromal cells (MSCs) are localized in a number of tissues and can be isolated and cultured in vitro. The above features determine the interest in MSCs as a perspective tool for additional therapy of various diseases [5,6,7,8]. It is assumed that upon entering the circulation, MSCs can follow the chemoattractant gradients and, reaching the area of damage, transmigrate through the vascular wall endothelium to the periendothelial space. It is this phenomenon that underlies the intravascular delivery of MSCs in cell therapy protocols [11,12,13]. It is obvious that interaction with endothelial cells (ECs) is one of the important factors that determine the fate of injected MSCs
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