Miro1 Enhances Mitochondria Transfer from Multipotent Mesenchymal Stem Cells (MMSC) to Neural Cells and Improves the Efficacy of Cell Recovery

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2018 Mar 23

PMID 29562677

Citations 95

Authors

Valentina A Babenko

Denis N Silachev

Vasily A Popkov

Ljubava D Zorova

Irina B Pevzner

Egor Y Plotnikov

Gennady T Sukhikh

Dmitry B Zorov

Affiliations

Soon will be listed here.

Abstract

A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage. We found that mitochondria were transferred from the MMSC to astrocytes in a more efficient manner when the astrocytes were exposed to ischemic damage associated with elevated ROS levels. Such transport of mitochondria restored the bioenergetics of the recipient cells and stimulated their proliferation. The introduction of MMSC with overexpressed Miro1 in animals that had undergone an experimental stroke led to significantly improved recovery of neurological functions. Our data suggest that mitochondrial impairment in differentiated cells can be compensated by receiving healthy mitochondria from MMSC. We demonstrate a key role of Miro1, which promotes the mitochondrial transfer from MMSC and suggest that the genetic modification of stem cells can improve the therapies for the injured brain.

Citing Articles

Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease.

Kiraly S, Stanley J, Eden E Antioxidants (Basel). 2025; 14(2).

PMID: 40002312 PMC: 11852311. DOI: 10.3390/antiox14020125.

Targeting mitochondrial transfer: a new horizon in cardiovascular disease treatment.

Zuo B, Li X, Xu D, Zhao L, Yang Y, Luan Y J Transl Med. 2024; 22(1):1160.

PMID: 39741312 PMC: 11687156. DOI: 10.1186/s12967-024-05979-x.

Astrocytic mitochondrial transfer to brain endothelial cells and pericytes increases with aging.

Velmurugan G, Vekaria H, Patel S, Sullivan P, Hubbard W J Cereb Blood Flow Metab. 2024; :271678X241306054.

PMID: 39668588 PMC: 11638933. DOI: 10.1177/0271678X241306054.

Protective effect of mesenchymal stromal cells in diabetic nephropathy: the In vitro and In vivo role of the M-Sec-tunneling nanotubes.

Barutta F, Corbetta B, Bellini S, Gambino R, Bruno S, Kimura S Clin Sci (Lond). 2024; 138(23):1537-1559.

PMID: 39535903 PMC: 11609313. DOI: 10.1042/CS20242064.

Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.

Irwin R, Thomas M, Fahey M, Mayan M, Smyth J, Delco M Stem Cell Res Ther. 2024; 15(1):359.

PMID: 39390589 PMC: 11468299. DOI: 10.1186/s13287-024-03932-9.

References

Osaka M, Honmou O, Murakami T, Nonaka T, Houkin K, Hamada H . Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome. Brain Res. 2010; 1343:226-35. DOI: 10.1016/j.brainres.2010.05.011. View

Spees J, Olson S, Whitney M, Prockop D . Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci U S A. 2006; 103(5):1283-8. PMC: 1345715. DOI: 10.1073/pnas.0510511103. View

Debattisti V, Gerencser A, Saotome M, Das S, Hajnoczky G . ROS Control Mitochondrial Motility through p38 and the Motor Adaptor Miro/Trak. Cell Rep. 2017; 21(6):1667-1680. PMC: 5710826. DOI: 10.1016/j.celrep.2017.10.060. View

Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C . Transfer of mitochondria from astrocytes to neurons after stroke. Nature. 2016; 535(7613):551-5. PMC: 4968589. DOI: 10.1038/nature18928. View

Caicedo A, Fritz V, Brondello J, Ayala M, Dennemont I, Abdellaoui N . MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function. Sci Rep. 2015; 5:9073. PMC: 4358056. DOI: 10.1038/srep09073. View

Nargesi A, Lerman L, Eirin A . Mesenchymal stem cell-derived extracellular vesicles for kidney repair: current status and looming challenges. Stem Cell Res Ther. 2017; 8(1):273. PMC: 5713024. DOI: 10.1186/s13287-017-0727-7. View

Longa E, Weinstein P, Carlson S, Cummins R . Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989; 20(1):84-91. DOI: 10.1161/01.str.20.1.84. View

Plotnikov E, Khryapenkova T, Vasileva A, Marey M, Galkina S, Isaev N . Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in co-culture. J Cell Mol Med. 2007; 12(5A):1622-31. PMC: 3918078. DOI: 10.1111/j.1582-4934.2007.00205.x. View

Jiang X, Mu D, Manabat C, Koshy A, Christen S, Tauber M . Differential vulnerability of immature murine neurons to oxygen-glucose deprivation. Exp Neurol. 2004; 190(1):224-32. DOI: 10.1016/j.expneurol.2004.07.010. View

10.

Silachev D, Uchevatkin A, Pirogov Y, Zorov D, Isaev N . Comparative evaluation of two methods for studies of experimental focal ischemia: magnetic resonance tomography and triphenyltetrazoleum detection of brain injuries. Bull Exp Biol Med. 2009; 147(2):269-72. DOI: 10.1007/s10517-009-0489-z. View

11.

Lai C, Breakefield X . Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Front Physiol. 2012; 3:228. PMC: 3384085. DOI: 10.3389/fphys.2012.00228. View

12.

Kumar R, Bukowski M, Wider J, Reynolds C, Calo L, Lepore B . Mitochondrial dynamics following global cerebral ischemia. Mol Cell Neurosci. 2016; 76:68-75. PMC: 5056829. DOI: 10.1016/j.mcn.2016.08.010. View

13.

Soane L, Li Dai W, Fiskum G, Bambrick L . Sulforaphane protects immature hippocampal neurons against death caused by exposure to hemin or to oxygen and glucose deprivation. J Neurosci Res. 2009; 88(6):1355-63. PMC: 3037525. DOI: 10.1002/jnr.22307. View

14.

Jolkkonen J, Puurunen K, Rantakomi S, Harkonen A, Haapalinna A, Sivenius J . Behavioral effects of the alpha(2)-adrenoceptor antagonist, atipamezole, after focal cerebral ischemia in rats. Eur J Pharmacol. 2000; 400(2-3):211-9. DOI: 10.1016/s0014-2999(00)00409-x. View

15.

Gerdes H, Rustom A, Wang X . Tunneling nanotubes, an emerging intercellular communication route in development. Mech Dev. 2012; 130(6-8):381-7. DOI: 10.1016/j.mod.2012.11.006. View

16.

Jian Z, Ding S, Deng H, Wang J, Yi W, Wang L . Probenecid protects against oxygen-glucose deprivation injury in primary astrocytes by regulating inflammasome activity. Brain Res. 2016; 1643:123-9. DOI: 10.1016/j.brainres.2016.05.002. View

17.

King M, Attardi G . Isolation of human cell lines lacking mitochondrial DNA. Methods Enzymol. 1996; 264:304-13. DOI: 10.1016/s0076-6879(96)64029-4. View

18.

Quintero O, DiVito M, Adikes R, Kortan M, Case L, Lier A . Human Myo19 is a novel myosin that associates with mitochondria. Curr Biol. 2009; 19(23):2008-13. PMC: 2805763. DOI: 10.1016/j.cub.2009.10.026. View

19.

Silachev D, Isaev N, Pevzner I, Zorova L, Stelmashook E, Novikova S . The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk. PLoS One. 2012; 7(12):e51553. PMC: 3522699. DOI: 10.1371/journal.pone.0051553. View

20.

Babenko V, Silachev D, Zorova L, Pevzner I, Khutornenko A, Plotnikov E . Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells. Stem Cells Transl Med. 2015; 4(9):1011-20. PMC: 4542870. DOI: 10.5966/sctm.2015-0010. View