Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria?
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 mitochondr...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7408 |
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| author | Ljubava D. Zorova Sergei I. Kovalchuk Vasily A. Popkov Valery P. Chernikov Anastasia A. Zharikova Anastasia A. Khutornenko Savva D. Zorov Konstantin S. Plokhikh Roman A. Zinovkin Ekaterina A. Evtushenko Valentina A. Babenko Irina B. Pevzner Yulia A. Shevtsova Kirill V. Goryunov Egor Y. Plotnikov Denis N. Silachev Gennady T. Sukhikh Dmitry B. Zorov |
| author_facet | Ljubava D. Zorova Sergei I. Kovalchuk Vasily A. Popkov Valery P. Chernikov Anastasia A. Zharikova Anastasia A. Khutornenko Savva D. Zorov Konstantin S. Plokhikh Roman A. Zinovkin Ekaterina A. Evtushenko Valentina A. Babenko Irina B. Pevzner Yulia A. Shevtsova Kirill V. Goryunov Egor Y. Plotnikov Denis N. Silachev Gennady T. Sukhikh Dmitry B. Zorov |
| author_sort | Ljubava D. Zorova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:47:16Z |
| format | Article |
| id | doaj.art-82f9802d02f142d898632e90f7fe0966 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:47:16Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-82f9802d02f142d898632e90f7fe09662023-11-23T20:13:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313740810.3390/ijms23137408Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria?Ljubava D. Zorova0Sergei I. Kovalchuk1Vasily A. Popkov2Valery P. Chernikov3Anastasia A. Zharikova4Anastasia A. Khutornenko5Savva D. Zorov6Konstantin S. Plokhikh7Roman A. Zinovkin8Ekaterina A. Evtushenko9Valentina A. Babenko10Irina B. Pevzner11Yulia A. Shevtsova12Kirill V. Goryunov13Egor Y. Plotnikov14Denis N. Silachev15Gennady T. Sukhikh16Dmitry B. Zorov17A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaA.P. Avtsyn Research Institute of Human Morphology, Moscow 117418, RussiaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaNational Research Center, “Kurchatov Institute”, Moscow 123182, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaBiological Faculty, Lomonosov Moscow State University, Moscow 119992, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, RussiaExtracellular 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.https://www.mdpi.com/1422-0067/23/13/7408stem cellsmesenchymal stromal cellsextracellular vesiclesexosomesectosomesmitochondria |
| spellingShingle | Ljubava D. Zorova Sergei I. Kovalchuk Vasily A. Popkov Valery P. Chernikov Anastasia A. Zharikova Anastasia A. Khutornenko Savva D. Zorov Konstantin S. Plokhikh Roman A. Zinovkin Ekaterina A. Evtushenko Valentina A. Babenko Irina B. Pevzner Yulia A. Shevtsova Kirill V. Goryunov Egor Y. Plotnikov Denis N. Silachev Gennady T. Sukhikh Dmitry B. Zorov Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria? International Journal of Molecular Sciences stem cells mesenchymal stromal cells extracellular vesicles exosomes ectosomes mitochondria |
| title | Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria? |
| title_full | Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria? |
| title_fullStr | Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria? |
| title_full_unstemmed | Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria? |
| title_short | Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria? |
| title_sort | do extracellular vesicles derived from mesenchymal stem cells contain functional mitochondria |
| topic | stem cells mesenchymal stromal cells extracellular vesicles exosomes ectosomes mitochondria |
| url | https://www.mdpi.com/1422-0067/23/13/7408 |
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