BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Primary astrocytic mitochondrial transplantation ameliorates ischemic stroke

  • Eun-Hye Lee (Hanyang Biomedical Research Institute) ;
  • Minkyung Kim (Department of Bioengineering, College of Engineering) ;
  • Seung Hwan Ko (Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Chun-Hyung Kim (Paean Biotechnology Inc.) ;
  • Minhyung Lee (Department of Bioengineering, College of Engineering) ;
  • Chang-Hwan Park (Hanyang Biomedical Research Institute)
  • Received : 2022.07.12
  • Accepted : 2022.09.14
  • Published : 2023.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Mitochondria are important organelles that regulate adenosine triphosphate production, intracellular calcium buffering, cell survival, and apoptosis. They play therapeutic roles in injured cells via transcellular transfer through extracellular vesicles, gap junctions, and tunneling nanotubes. Astrocytes can secrete numerous factors known to promote neuronal survival, synaptic formation, and plasticity. Recent studies have demonstrated that astrocytes can transfer mitochondria to damaged neurons to enhance their viability and recovery. In this study, we observed that treatment with mitochondria isolated from rat primary astrocytes enhanced cell viability and ameliorated hydrogen peroxide-damaged neurons. Interestingly, isolated astrocytic mitochondria increased the number of cells under damaged neuronal conditions, but not under normal conditions, although the mitochondrial transfer efficiency did not differ between the two conditions. This effect was also observed after transplanting astrocytic mitochondria in a rat middle cerebral artery occlusion model. These findings suggest that mitochondria transfer therapy can be used to treat acute ischemic stroke and other diseases.

Keywords

Acknowledgement

The Individual Basic Science and Engineering Research Program (2019R1A2C2005681) of the National Research Foundation funded by the Ministry of Science and ICT in Korea supported this work.

References

  1. Paul S and Candelario-Jalil E (2021) Emerging neuroprotective strategies for the treatment of ischemic stroke: an overview of clinical and preclinical studies. Exp Neurol 335, 113518
  2. Bakthavachalam P and Shanmugam PST (2017) Mitochondrial dysfunction - silent killer in cerebral ischemia. J Neurol Sci 375, 417-423 https://doi.org/10.1016/j.jns.2017.02.043
  3. Nunnari J and Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148, 1145-1159 https://doi.org/10.1016/j.cell.2012.02.035
  4. Karbowski M and Neutzner A (2012) Neurodegeneration as a consequence of failed mitochondrial maintenance. Acta Neuropathol 123, 157-171 https://doi.org/10.1007/s00401-011-0921-0
  5. McBride HM, Neuspiel M and Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16, R551-R560 https://doi.org/10.1016/j.cub.2006.06.054
  6. Fecher C, Trovo L, Muller SA et al (2019) Cell-typespecific profiling of brain mitochondria reveals functional and molecular diversity. Nat Neurosci 22, 1731-1742 https://doi.org/10.1038/s41593-019-0479-z
  7. Chang CY, Liang MZ and Chen L (2019) Current progress of mitochondrial transplantation that promotes neuronal regeneration. Transl Neurodegener 8, 17
  8. Konari N, Nagaishi K, Kikuchi S et al (2019) Mitochondria transfer from mesenchymal stem cells structurally and functionally repairs renal proximal tubular epithelial cells in diabetic nephropathy in vivo. Sci Rep 9, 5184
  9. Pourmohammadi-Bejarpasi Z, Roushandeh AM, Saberi A et al (2020) Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model. Brain Res Bull 165, 70-80 https://doi.org/10.1016/j.brainresbull.2020.09.018
  10. Robicsek O, Ene HM, Karry R et al (2018) Isolated mitochondria transfer improves neuronal differentiation of schizophrenia-derived induced pluripotent stem cells and rescues deficits in a rat model of the disorder. Schizophr Bull 44, 432-442 https://doi.org/10.1093/schbul/sbx077
  11. Freeman MR and Rowitch DH (2013) Evolving concepts of gliogenesis: a look way back and ahead to the next 25 years. Neuron 80, 613-623 https://doi.org/10.1016/j.neuron.2013.10.034
  12. Verkhratsky A, Matteoli M, Parpura V et al (2016) Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion. EMBO J 35, 239-257 https://doi.org/10.15252/embj.201592705
  13. Jones EV and Bouvier DS (2014) Astrocyte-secreted matricellular proteins in CNS remodelling during development and disease. Neural Plast 2014, 321209
  14. Hayakawa K, Esposito E, Wang X et al (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535, 551-555 https://doi.org/10.1038/nature18928
  15. Nistico R, Piccirilli S, Cucchiaroni ML et al (2008) Neuroprotective effect of hydrogen peroxide on an in vitro model of brain ischaemia. Br J Pharmacol 153, 1022-1029 https://doi.org/10.1038/sj.bjp.0707587
  16. Mut M, Yemisci M, Gursoy-Ozdemir Y et al (2009) Hydrogen peroxide-induced stroke: elucidation of the mechanism in vivo. J Neurosurg 110, 94-100 https://doi.org/10.3171/2008.3.17434
  17. Cabreira V and Massano J (2019) Parkinson's disease: clinical review and update. Acta Med Port 32, 661-670 https://doi.org/10.20344/amp.11978
  18. Jankovic J and Poewe W (2012) Therapies in Parkinson's disease. Curr Opin Neurol 25, 433-447 https://doi.org/10.1097/WCO.0b013e3283542fc2
  19. Park CH, Kang JS, Kim JS et al (2006) Differential actions of the proneural genes encoding Mash1 and neurogenins in Nurr1-induced dopamine neuron differentiation. J Cell Sci 119, 2310-2320 https://doi.org/10.1242/jcs.02955
  20. Ding YM, Jaumotte JD, Signore AP et al (2004) Effects of 6-hydroxydopamine on primary cultures of substantia nigra: specific damage to dopamine neurons and the impact of glial cell line-derived neurotrophic factor. J Neurochem 89, 776-787 https://doi.org/10.1111/j.1471-4159.2004.02415.x
  21. Lightowlers RN, Chrzanowska-Lightowlers ZM and Russell OM (2020) Mitochondrial transplantation-a possible therapeutic for mitochondrial dysfunction?: mitochondrial transfer is a potential cure for many diseases but proof of efficacy and safety is still lacking. EMBO Rep 21, e50964
  22. Yang JL, Mukda S and Chen SD (2018) Diverse roles of mitochondria in ischemic stroke. Redox Biol 16, 263-275 https://doi.org/10.1016/j.redox.2018.03.002
  23. He Z, Ning N, Zhou Q et al (2020) Mitochondria as a therapeutic target for ischemic stroke. Free Radic Biol Med 146, 45-58 https://doi.org/10.1016/j.freeradbiomed.2019.11.005
  24. Berridge MV, Schneider RT and McConnell MJ (2016) Mitochondrial transfer from astrocytes to neurons following ischemic insult: guilt by association? Cell Metab 24, 376-378 https://doi.org/10.1016/j.cmet.2016.08.023
  25. Moon HE and Paek SH (2015) Mitochondrial dysfunction in Parkinson's disease. Exp Neurobiol 24, 103-116 https://doi.org/10.5607/en.2015.24.2.103