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Stem Cell Exosomes Improve Survival of Neural Stem Cells after Radiation Exposure

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Bulletin of Experimental Biology and Medicine Aims and scope

The death of neural stem cells in the hippocampus during radiation therapy of brain tumors leads to neurogenesis impairment and the development of cognitive dysfunctions at delayed terms after irradiation. Exosomes secreted by stem cells can provide a protective effect on neural stem cells. We isolated and characterized exosomes from the medium conditioned by neural stem cells and mesenchymal stem cells from mouse adipose tissue and studied their efficiency in protecting irradiated neural stem cells. According to dynamic light scattering data, the exosome size varied from 44 to 68 nm for neural stem cells, and from 80 to 130 nm for mesenchymal stem cells. All exosomes carried markers CD9, CD63, and TSG101. The survival rate and clonogenic activity of neural stem cells irradiated in a dose of 1 Gy was found to increase after culturing in the presence of stem cell exosome preparations.

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References

  1. 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

  2. Rodina AV, Semochkina YP, Vysotskaya OV, Glukhov AI, Moskaleva EYu. Features of long-term cultured adipose tissue-derived mesenchymal stem cells response to γ-irradiation. Radiats. Biol. Radioekol. 2019;59(3):243-254. Russian.

  3. Acharya MM, Martirosian V, Christie LA, Riparip L, Strnadel J, Parihar VK, Limoli CL. Defining the optimal window for cranial transplantation of human induced pluripotent stem cell-derived cells to ameliorate radiation-induced cognitive impairment. Stem Cells Transl. Med. 2015;4(1):74-83. https://doi.org/10.5966/sctm.2014-0063

    Article  CAS  PubMed  Google Scholar 

  4. 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 

  5. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Müller FJ, Loring JF, Yamasaki TR, Poon WW, Green KN, LaFerla FM. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc. Natl Acad. Sci. USA. 2009;106(32):13594-13599. https://doi.org/10.1073/pnas.0901402106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bonafede R, Scambi I, Peroni D, Potrich V, Boschi F, Benati D, Bonetti B, Mariotti R. Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis. Exp. Cell Res. 2016;340(1):150-158. https://doi.org/10.1016/j.yexcr.2015.12.009.

    Article  CAS  PubMed  Google Scholar 

  7. Chu C, Gao Y, Lan X, Lin J, Thomas AM, Li S. Stem-cell therapy as a potential strategy for radiation-induced brain injury. Stem Cell Rev. Rep. 2020;16(4):639-649. https://doi.org/10.1007/s12015-020-09984-7

    Article  PubMed  Google Scholar 

  8. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014;30:255-289. https://doi.org/10.1146/annurev-cellbio-101512-122326

    Article  CAS  PubMed  Google Scholar 

  9. Farinazzo A, Turano E, Marconi S, Bistaffa E, Bazzoli E, Bonetti B. Murine adipose-derived mesenchymal stromal cell vesicles: in vitro clues for neuroprotective and neuroregenerative approaches. Cytotherapy. 2015;17(5):571-578. https://doi.org/10.1016/j.jcyt.2015.01.005

    Article  CAS  PubMed  Google Scholar 

  10. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD. Radiation-induced brain injury: a review.Front. Oncol. 2012;2:73. https://doi.org/10.3389/fonc.2012.00073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm. Sin B. 2016;6(4):287-296. https://doi.org/10.1016/j.apsb.2016.02.001

    Article  PubMed  PubMed Central  Google Scholar 

  12. Haus DL, López-Velázquez L, Gold EM, Cunningham KM, Perez H, Anderson AJ, Cummings BJ. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury. Exp. Neurol. 2016;281:1-16. https://doi.org/10.1016/j.expneurol.2016.04.008

    Article  CAS  PubMed  Google Scholar 

  13. 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 

  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. Kowal J, Tkach M, Théry C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol. 2014;29:116-125. https://doi.org/10.1016/j.ceb.2014.05.004

    Article  CAS  PubMed  Google Scholar 

  16. 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 

  17. 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

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, Gho YS, Kurochkin IV, Mathivanan S, Quesenberry P, Sahoo S, Tahara H, Wauben MH, Witwer KW, Théry C. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles. 2014;3:26913. https://doi.org/10.3402/jev.v3.26913

    Article  PubMed  Google Scholar 

  19. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J. Proteomics. 2010;73(10):1907-1920. https://doi.org/10.1016/j.jprot.2010.06.006

    Article  CAS  PubMed  Google Scholar 

  20. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles. 2018;7(1):1535750. https://doi.org/10.1080/20013078.2018.1535750

  21. 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 Central  Google Scholar 

  22. Ratushnyak MG, Semochkina YP, Zhirnik AS, Smirnova OD. Improved survival and regeneration of irradiated mouse neural stem cells after co-culturing with non-irradiated mouse neural stem cells or mesenchymal stem cells from the adipose tissue. Bull. Exp. Biol. Med. 2021;172(2):228-235. https://doi.org/10.1007/s10517-021-05368-0

    Article  CAS  PubMed  Google Scholar 

  23. Shtam TA, Samsonov RA, Volnitskiy AV, Kamyshinsky RA, Verlov NA, Kniazeva MS, Korobkina EA, Orehov AS, Vasiliev AL, Konevega AL, Malek AV. Isolation of extracellular micro-vesicles from cell culture medium: comparative evaluation of methods. Biomed. Khim. 2018;64(1):23-30. https://doi.org/10.18097/PBMC20186401023

    Article  CAS  PubMed  Google Scholar 

  24. 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 

  25. Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of content, stoichiometry and transfer of miRNA from human neural stem cell line derived exosomes. PLoS One. 2016;11(1):e0146353. https://doi.org/10.1371/journal.pone.0146353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 2006. Chapter 3:Unit 3.22. https://doi.org/10.1002/0471143030.cb0322s30

  27. 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 

  28. Tseng AM, Chung DD, Pinson MR, Salem NA, Eaves SE, Miranda RC. Ethanol exposure increases miR-140 in extracellular vesicles: implications for fetal neural stem cell proliferation and maturation. Alcohol. Clin. Exp. Res. 2019;43(7):1414-1426. https://doi.org/10.1111/acer.14066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim. Biophys. Acta. 2012;1820(7):940-948. https://doi.org/10.1016/j.bbagen.2012.03.017

    Article  CAS  PubMed  Google Scholar 

  30. Vogel A, Upadhya R, Shetty AK. Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders. EBioMedicine. 2018;38:273-282. https://doi.org/10.1016/j.ebiom.2018.11.026

    Article  PubMed  PubMed Central  Google Scholar 

  31. Webb RL, Kaiser EE, Scoville SL, Thompson TA, Fatima S, Pandya C, Sriram K, Swetenburg RL, Vaibhav K, Arbab AS, Baban B, Dhandapani KM, Hess DC, Hoda MN, Stice SL. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model. Transl. Stroke Res. 2018;9(5):530-539. https://doi.org/10.1007/s12975-017-0599-2

    Article  CAS  PubMed  Google Scholar 

  32. Witwer KW, Buzás EI, Bemis LT, Bora A, Lässer C, Lötvall J, Nolte-’t Hoen EN, Piper MG, Sivaraman S, Skog J, Théry C, Wauben MH, Hochberg F. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles. 2013;2. https://doi.org/10.3402/jev.v2i0.20360

  33. Witwer KW, Soekmadji C, Hill AF, Wauben MH, Buzás EI, Di Vizio D, Falcon-Perez JM, Gardiner C, Hochberg F, Kurochkin IV, Lötvall J, Mathivanan S, Nieuwland R, Sahoo S, Tahara H, Torrecilhas AC, Weaver AM, Yin H, Zheng L, Gho YS, Quesenberry P, Théry C. Updating the MISEV minimal requirements for extracellular vesicle studies: building bridges to reproducibility. J. Extracell. Vesicles. 2017;6(1):1396823. https://doi.org/10.1080/20013078.2017.1396823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, Shang X, Zhang ZG, Chopp M. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells. 2012;30(7):1556-1564. https://doi.org/10.1002/stem.1129

    Article  CAS  PubMed  Google Scholar 

  35. Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, Xiong Y. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J. Neurosurg. 2015;122(4):856-867. https://doi.org/10.3171/2014.11.JNS14770

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhang Y, Zhang Y, Chopp M, Zhang ZG, Mahmood A, Xiong Y. Mesenchymal stem cell-derived exosomes improve functional recovery in rats after traumatic brain injury: a dose-response and therapeutic window study. Neurorehabil. Neural Repair. 2020;34(7):616-626. https://doi.org/10.1177/1545968320926164

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. National Research Center “Kurchatov Institute”, Moscow, Russia

    M. G. Ratushnyak, Yu. P. Semochkina, E. V. Yastremsky & R. A. Kamyshinsky

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  1. M. G. Ratushnyak
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  2. Yu. P. Semochkina
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  3. E. V. Yastremsky
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  4. R. A. Kamyshinsky
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Correspondence to M. G. Ratushnyak.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 100-108, June, 2022

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Ratushnyak, M.G., Semochkina, Y.P., Yastremsky, E.V. et al. Stem Cell Exosomes Improve Survival of Neural Stem Cells after Radiation Exposure. Bull Exp Biol Med 173, 544–552 (2022). https://doi.org/10.1007/s10517-022-05587-z

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