Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

Influence of olive oil and its components on mesenchymal stem cell biology

Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging,due to the antioxidant capacity and capability of its components to modulate cellular signaling pathways.Consumption of olive oil can alter the physiology of mesenchymal stem cells(MSCs).This may explain part of the healthy effects of olive oil consumption,such as prevention of unwanted aging processes.To date,there are no specific studies on the action of olive oil on MSCs,but effects of many components of such food on cell viability and differentiation have been evaluated.The objective of this article is to review existing literature on how different compounds of extra virgin olive oil,including residues of fatty acids,vitamins,squalene,triterpenes,pigments and phenols,affect MSC maintenance and differentiation,in order to provide a better understanding of the healthy effects of this food.Interestingly,most studies have shown a positive effect of these compounds on MSCs.The collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.