Skip to main content
Log in

The Use of Neural Stem Cells-Derived Exosomes to Prevent Late Radiation-Induced Cognitive Impairments in Mice

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of intranasal administration of neural stem cell (NSC)-derived exosomes on behavior and cognitive functions of mice in the late period after head irradiation in a dose of 8 Gy. The used exosomes had specific markers (CD9+/CD63+, 99.5%; TSG101+, 98.4%) and mean size 105.7±8.8 nm according to dynamic light scattering data and 119.0±12.4 nm according to nanoparticle tracking analysis (NTA). Exosome suspension (2×1012 particles/ml according to NTA measurements) was administered intranasally for 4 weeks starting from 48 h after irradiation in a volume of 5 μl/nostril (2×1010 exosomes/mouse). It was shown that intranasal administration of mouse NSC-derived exosomes prevented delayed radiation-induced behavioral changes and recognition memory impairments in mice after head irradiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Pazzaglia S, Briganti G, Mancuso M, Saran A. Neurocognitive decline following radiotherapy: mechanisms and therapeutic implications. Cancers (Basel). 2020;12(1):146. https://doi.org/10.3390/cancers12010146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Posypanova GA, Ratushnyak MG, Semochkina YP, Abisheva AA, Moskaleva EYu. The sensitivity of the cultured murine neural stem cells to the ionizing radiation. Tsitologiya. 2019;61(10):806-816. Russian. https://doi.org/10.1134/S0041377119100067

  3. Posypanova GA, Ratushnyak MG, Semochkina YP, Strepetov AN. Response of murine neural stem/progenitor cells to gamma-neutron radiation. Int. J. Radiat. Biol. 2022;98(10):1559-1570. https://doi.org/10.1080/09553002.2022.2055802

    Article  CAS  PubMed  Google Scholar 

  4. Hladik D, Tapio S. Effects of ionizing radiation on the mammalian brain. Mutat. Res. Rev. Mutat. Res. 2016;770(Pt B):219-230. https://doi.org/10.1016/j.mrrev.2016.08.003

    Article  CAS  PubMed  Google Scholar 

  5. Zhirnik AS, Smirnova OD, Semochkina JuP, Shibaeva KD, Rodina AV, Ratushnjak MG, Moskaleva EJu. Cognitive impairment and induction of neuroinflammation in the late period after single whole brain γ-irradiation of mice. Radiats. Biol. Radioekol. 2021;61(1):32-43. Russian. https://doi.org/10.31857/S0869803121010112

  6. Ratushnyak MG, Semochkina YP, Yastremsky EV, Kamyshinsky RA. Stem Cell Exosomes Improve Survival of Neural Stem Cells after Radiation Exposure. Bull. Exp. Biol. Med. 2022;173(4):544-552. https://doi.org/10.1007/s10517-022-05587-z

    Article  CAS  PubMed  Google Scholar 

  7. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2002;2(8):569-579. https://doi.org/10.1038/nri855

    Article  CAS  PubMed  Google Scholar 

  8. Silachev DN, Goryunov KV, Shpilyuk MA, Beznoschenko OS, Morozova NY, Kraevaya EE, Popkov VA, Pevzner IB, Zorova LD, Evtushenko EA, Starodubtseva NL, Kononikhin AS, Bugrova AE, Evtushenko EG, Plotnikov EY, Zorov DB, Sukhikh GT. Effect of MSCs and MSC-derived extracellular vesicles on human blood coagulation. Cells. 2019;8(3):258. https://doi.org/10.3390/cells8030258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cone AS, Yuan X, Sun L, Duke LC, Vreones MP, Carrier AN, Kenyon SM, Carver SR, Benthem SD, Stimmell AC, Moseley SC, Hike D, Grant SC, Wilber AA, Olcese JM, Meckes DG Jr. Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer’s disease-like phenotypes in a preclinical mouse model. Theranostics. 2021;11(17):8129-8142. https://doi.org/10.7150/thno.62069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu M, Yang Y, Zhao B, Yang Y, Wang J, Shen K, Yang X, Hu D, Zheng G, Han J. Exosomes derived from adipose-derived mesenchymal stem cells ameliorate radiation-induced brain injury by activating the SIRT1 pathway. Front. Cell Dev. Biol. 2021;9:693782. https://doi.org/10.3389/fcell.2021.693782

  11. Long Q, Upadhya D, Hattiangady B, Kim DK, An SY, Shuai B, Prockop DJ, Shetty AK. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc. Natl Acad. Sci. USA. 2017;114(17):E3536-E3545. https://doi.org/10.1073/pnas.1703920114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Turovsky EA, Golovicheva VV, Varlamova EG, Danilina TI, Goryunov KV, Shevtsova YA, Pevzner IB, Zorova LD, Babenko VA, Evtushenko EA, Zharikova AA, Khutornenko AA, Kovalchuk SI, Plotnikov EY, Zorov DB, Sukhikh GT, Silachev DN. Mesenchymal stromal cell-derived extracellular vesicles afford neuroprotection by modulating PI3K/AKT pathway and calcium oscillations. Int. J. Biol. Sci. 2022;18(14):5345-5368. https://doi.org/10.7150/ijbs.73747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Baulch JE, Acharya MM, Allen BD, Ru N, Chmielewski NN, Martirosian V, Giedzinski E, Syage A, Park AL, Benke SN, Parihar VK, Limoli CL. Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain. Proc. Natl Acad. Sci. USA. 2016;113(17):4836-4841. https://doi.org/10.1073/pnas.1521668113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ioannides P, Giedzinski E, Limoli CL. Evaluating different routes of extracellular vesicle administration for cranial therapies. J. Cancer Metastasis Treat. 2020;6(15). https://doi.org/10.20517/2394-4722.2020.22

  15. Smith SM, Giedzinski E, Angulo MC, Lui T, Lu C, Park AL, Tang S, Martirosian V, Ru N, Chmielewski NN, Liang Y, Baulch JE, Acharya MM, Limoli CL. Functional equivalence of stem cell and stem cell-derived extracellular vesicle transplantation to repair the irradiated brain. Stem Cells Transl Med. 2020;9(1):93-105. https://doi.org/10.1002/sctm.18-0227

    Article  CAS  PubMed  Google Scholar 

  16. Katelnikova AE, Kryshen KL, Zueva AA, Makarova MN. Intranasal introduction to laboratory animals. Lab. Zhivotn. Nauch. Issled. 2019;(2):9. Russian. https://doi.org/10.29296/2618723X-2019-02-09

  17. Friard O, Gamba M. BORIS: A free, versatile open-source event-logging software for video/audio coding and live observations. Methods Ecol. Evol. 2016;7(11):1325-1330. https://doi.org/10.1111/2041-210X.12584

    Article  Google Scholar 

  18. Posypanova GA, Ratushnyak MG, Vysotskaya OV, Glukhov AI, Semochkina YuP, Rodina AV, Moskaleva EYu. Protection of neural stem cells from genotoxic effects by factors secreted by mesenchymal stem cells. Mol. Med. 2018;16(6):28-34. Russian. https://doi.org/10.29296/24999490-2018-06-05

  19. Leavitt RJ, Acharya MM, Baulch JE, Limoli CL. Extracellular vesicle-derived miR-124 resolves radiation-induced brain injury. Cancer Res. 2020;80(19):4266-4277. https://doi.org/10.1158/0008-5472.CAN-20-1599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shekari F, Nazari A, Assar Kashani S, Hajizadeh-Saffar E, Lim R, Baharvand H. Pre-clinical investigation of mesenchymal stromal cell-derived extracellular vesicles: a systematic review. Cytotherapy. 2021;23(4):277-284. https://doi.org/10.1016/j.jcyt.2020.12.009

    Article  CAS  PubMed  Google Scholar 

  21. Ezquer F, Quintanilla ME, Morales P, Santapau D, Ezquer M, Kogan MJ, Salas-Huenuleo E, Herrera-Marschitz M, Israel Y. Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking. Addict. Biol. 2019;24(5):994-1007. https://doi.org/10.1111/adb.12675

    Article  CAS  PubMed  Google Scholar 

  22. Losurdo M, Pedrazzoli M, D’Agostino C, Elia CA, Massenzio F, Lonati E, Mauri M, Rizzi L, Molteni L, Bresciani E, Dander E, D’Amico G, Bulbarelli A, Torsello A, Matteoli M, Buffelli M, Coco S. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer’s disease. Stem Cells Transl. Med. 2020;9(9):1068-1084. https://doi.org/10.1002/sctm.19-0327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Perets N, Oron O, Herman S, Elliott E, Offen D. Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B. Mol. Autism. 2020;11(1):65. https://doi.org/10.1186/s13229-020-00366-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Spinelli M, Natale F, Rinaudo M, Leone L, Mezzogori D, Fusco S, Grassi C. Neural stem cell-derived exosomes revert HFD-dependent memory impairment via CREB-BDNF signalling. Int. J. Mol. Sci. 2020;21(23):8994. https://doi.org/10.3390/ijms21238994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhdanova DY, Poltavtseva RA, Svirshchevskaya EV, Bobkova NV. Effect of Intranasal Administration of Multipotent Mesenchymal Stromal Cell Exosomes on Memory of Mice in Alzheimer’s Disease Model. Bull. Exp. Biol. Med. 2021;170(4):575-582. https://doi.org/10.1007/s10517-021-05109-3

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. G. Ratushnyak.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 261-268, December, 2022

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ratushnyak, M.G., Zhirnik, A.S., Smirnova, O.D. et al. The Use of Neural Stem Cells-Derived Exosomes to Prevent Late Radiation-Induced Cognitive Impairments in Mice. Bull Exp Biol Med 174, 571–577 (2023). https://doi.org/10.1007/s10517-023-05749-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-023-05749-7

Key Words

Navigation