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

Autor: Zorova LD; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Kovalchuk SI; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia., Popkov VA; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Chernikov VP; A.P. Avtsyn Research Institute of Human Morphology, Moscow 117418, Russia., Zharikova AA; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia., Khutornenko AA; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Zorov SD; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia., Plokhikh KS; National Research Center, 'Kurchatov Institute', Moscow 123182, Russia., Zinovkin RA; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia., Evtushenko EA; Biological Faculty, Lomonosov Moscow State University, Moscow 119992, Russia., Babenko VA; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Pevzner IB; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Shevtsova YA; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia., Goryunov KV; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Plotnikov EY; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Silachev DN; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Sukhikh GT; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia., Zorov DB; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.; V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jul 03; Vol. 23 (13). Date of Electronic Publication: 2022 Jul 03.
DOI: 10.3390/ijms23137408
Abstrakt: 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.
Databáze: MEDLINE
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