Extracellular Vehicles of Oxygen-Depleted Mesenchymal Stromal Cells: Route to Off-Shelf Cellular Therapeutics?

Abstract

Cellular therapy is a promising tool of human medicine to successfully treat complex and challenging pathologies such as cardiovascular diseases or chronic inflammatory conditions. Bone marrow-derived mesenchymal stromal cells (BMSCs) are in the limelight of these efforts, initially, trying to exploit their natural properties by direct transplantation. Extensive research on the therapeutic use of BMSCs shed light on a number of key aspects of BMSC physiology including the importance of oxygen in the control of BMSC phenotype. These efforts also led to a growing number of evidence indicating that the beneficial therapeutic effects of BMSCs can be mediated by BMSC-secreted agents. Further investigations revealed that BMSC-excreted extracellular vesicles could mediate the potentially therapeutic effects of BMSCs. Here, we review our current understanding of the relationship between low oxygen conditions and the effects of BMSC-secreted extracellular vesicles focusing on the possible medical relevance of this interplay.

Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease

“…Preconditioning includes parent cell manipulations using specific culturing conditions, such as hypoxia, 3D culturing, and serum deprivation. Biochemical stimuli, including lipopolysaccharides, nitric oxide, and proinflammatory cytokines and exogenous genes such as plasmid DNA and miRNAs, can also be introduced into the culturing environment [129][130][131].…”