Extracellular Vesicles Isolated from Mesenchymal Stromal Cells Primed with Hypoxia: Novel Strategy in Regenerative Medicine.

Mesenchymal stromal cells (MSCs) regulate other cell types through a strong paracrine component called the secretome, comprising several bioactive entities. The composition of the MSCs' secretome is dependent upon the microenvironment in which they thrive, and hence, it could be altered by pre-conditioning the MSCs during in vitro culture. The primary aim of this review is to discuss various strategies that are being used for the pre-conditioning of MSCs, also known as "priming of MSCs", in the context of improving their therapeutic potential. Several studies have underscored the importance of extracellular vesicles (EVs) derived from primed MSCs in improving their efficacy for the treatment of various diseases. We have previously shown that co-culturing hematopoietic stem cells (HSCs) with hypoxia-primed MSCs improves their engraftment potential. Now the question we pose is, would priming of MSCs with hypoxia favorably alter their secretome? and would this altered secretome work as effectively as the cell to cell contact did? Here we review the current strategies of using the secretome, specifically the EVs (microvesicles and exosomes), collected from the primed MSCs with the intention of expanding HSCs ex vivo. We speculate that effective priming of MSCs in vitro could modulate the molecular profile of their secretome, which could eventually be used as a cell-free biologic in clinical settings.