Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria?

Abstract

Extracellular vesicles (EV) derived from stem cells have become an effective complement to the use in cell therapy of stem cells themselves, which has led to an explosion of research into the mechanisms of vesicle formation and their action. There is evidence demonstrating the presence of mitochondrial components in EV, but a definitive conclusion about whether EV contains fully functional mitochondria has not yet been made. In this study, two EV fractions derived from mesenchymal stromal stem cells (MSC) and separated by their size were examined. Flow cytometry revealed the presence of mitochondrial lipid components capable of interacting with mitochondrial dyes MitoTracker Green and 10-nonylacridine orange; however, the EV response to the probe for mitochondrial membrane potential was negative. Detailed analysis revealed components from all mitochondria compartments, including house-keeping mitochondria proteins and DNA as well as energy-related proteins such as membrane-localized proteins of complexes I, IV, and V, and soluble proteins from the Krebs cycle. When assessing the functional activity of mitochondria, high variability in oxygen consumption was noted, which was only partially attributed to mitochondrial respiratory activity. Our findings demonstrate that the EV contain all parts of mitochondria; however, their independent functionality inside EV has not been confirmed, which may be due either to the absence of necessary cofactors and/or the EV formation process and, probably the methodology of obtaining EV.

Extracellular Vesicles in Sickle Cell Disease: A Promising Tool

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The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles

“…Emerging evidence indicates the presence of mitochondrial components in EVs [ 40 ]. As known, Glo2 is also located in the mitochondrion [ 7 ], which might suggest a mitochondrial origin for EV-embedded Glo2.…”

“…Recently, Hsp27 have been found to be exported by exosomes, playing a key role in cell-to-cell communication, signaling, immunity, and inflammation. Interestingly, Hsp27 also plays a pivotal role in the biogenesis of exosomes [ 40 ]. We speculate that MG-modified Hsp27 may be endowed with a major functionality in performing the above-mentioned biological roles, which remain to be demonstrated.…”

From Promise to Reality: Bioengineering Strategies to Enhance the Therapeutic Potential of Extracellular Vesicles

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