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In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles

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Abstract

Triticum aestivum plant extracts are often used as a natural healer in traditional medicine but which particles mainly have role in these processes are not scientifically proven. In other words, no attempts have been made to investigate the effects of wheat exosomes in regenerative medicine applications or drug development up to now. The current study was first time performed to demonstrate the activity of wheat exosomes in wound healing process using in vitro approaches. Although its fundamental wound healing process remains a mystery, in the current study, the efficiency of wheat grass juice–derived exosomes on cell viability and migration was examined. Increasing concentrations up to 200 μg/mL of the wheat exosome have yielded astonishing proliferative and migratory effects on endothelial, epithelial, and dermal fibroblast cells. RT-PCR analysis also showed collagen type I; mRNA levels were approximately twofold higher in expression after treating with 200 μg/mL wheat exosome. Additionally, Annexin V staining of apoptotic cells accompanied with the cell cycle analysis resulted with the reduction of the apoptotic cell number with no dispersion to the cell cycle analysis while plant exosomes have also increased tube-like structure formation of the endothelial cells. All in all, this research suggests a brand-new opening for skin wound healing therapy strategy by using wheat-derived exosomes due to its proliferative and migratory characteristics. Plant exosomes require a further research both clinically and in in vivo for wound healing drug development. Moreover, plant exosome therapy strategies would be safer and economical alternative for clinical wound healing.

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References

  1. Yates, C. C., Hebda, P., & Wells, A. (2012). Skin wound healing and scarring: fetal wounds and regenerative restitution. Birth Defects Research Part C - Embryo Today: Reviews, 96(4), 325–333. https://doi.org/10.1002/bdrc.21024.

    Article  CAS  Google Scholar 

  2. Balekar, N., Katkam, N. G., Nakpheng, T., Jehtae, K., & Srichana, T. (2012). Evaluation of the wound healing potential of Wedelia trilobata (L.) leaves. Journal of Ethnopharmacology, 141(3), 817–824. https://doi.org/10.1016/j.jep.2012.03.019.

    Article  PubMed  Google Scholar 

  3. Corrado, C., Raimondo, S., Chiesi, A., Ciccia, F., De Leo, G., & Alessandro, R. (2013). Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. International Journal of Molecular Sciences, 14(3), 5338–5366. https://doi.org/10.3390/ijms14035338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Simons, M., & Raposo, G. (2009). Exosomes--vesicular carriers for intercellular communication. Current Opinion in Cell Biology, 21(4), 575–581. https://doi.org/10.1016/j.ceb.2009.03.007.

    Article  CAS  PubMed  Google Scholar 

  5. Zech, D., Rana, S., Büchler, M. W., & Zöller, M. (2012). Tumor-exosomes and leukocyte activation: an ambivalent crosstalk. Cell Communication and Signaling, 10(1), 37. https://doi.org/10.1186/1478-811X-10-37.

    Article  CAS  PubMed  Google Scholar 

  6. Théry, C., Regnault, A., Garin, J., Wolfers, J., Zitvogel, L., Ricciardi-Castagnoli, P., Raposo, G., & Amigorena, S. (1999). Molecular characterization of dendritic cell-derived exosomes. The Journal of Cell Biology, 147(3), 599–610. https://doi.org/10.1083/jcb.147.3.599.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lai, R. C., Arslan, F., Lee, M. M., Sze, S. K., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., el Oakley, R. M., Pasterkamp, G., de Kleijn, D. P. V., & Lim, S. K. (2010). Addendum to exosome secreted by MSC reduces myocardial ischemia/reperfusion injury [Stem Cell Research, 4, (2010), 214-222]. Stem Cell Research, 5(2), 170–171. https://doi.org/10.1016/j.scr.2010.05.003.

    Article  CAS  Google Scholar 

  8. Mallegol, J., Van Niel, G., Lebreton, C., Lepelletier, Y., Candalh, C., Dugave, C., et al. (2007). T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology, 132(5), 1866–1876. https://doi.org/10.1053/j.gastro.2007.02.043.

    Article  CAS  PubMed  Google Scholar 

  9. Kapsogeorgou, E. K., Abu-Helu, R. F., Moutsopoulos, H. M., & Manoussakis, M. N. (2005). Salivary gland epithelial cell exosomes: a source of autoantigenic ribonucleoproteins. Arthritis and Rheumatism, 52(5), 1517–1521. https://doi.org/10.1002/art.21005.

    Article  CAS  PubMed  Google Scholar 

  10. Ristorcelli, E., Beraud, E., Verrando, P., Villard, C., Lafitte, D., Sbarra, V., et al. (2008). Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. The FASEB Journal, 22(9), 3358–3369. https://doi.org/10.1096/fj.07-102855.

    Article  CAS  PubMed  Google Scholar 

  11. Lin, J., Li, J., Huang, B., Liu, J., Chen, X., Chen, X.-M., Xu, Y. M., Huang, L. F., & Wang, X.-Z. (2015). Exosomes: novel biomarkers for clinical diagnosis. The Scientific World Journal, 2015, 1–8. https://doi.org/10.1155/2015/657086.

    Article  CAS  Google Scholar 

  12. Raimondo, S., Naselli, F., Fontana, S., Monteleone, F., Lo Dico, A., Saieva, L., et al. (2015). Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget, 6(23), 19514–19527. https://doi.org/10.18632/oncotarget.4004.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Allmang, C., Kufel, J., Chanfreau, G., Mitchell, P., Petfalski, E., & Tollervey, D. (1999). Functions of the exosome in rRNA, snoRNA and snRNA synthesis. EMBO Journal, 18(19), 5399–5410. https://doi.org/10.1093/emboj/18.19.5399.

  14. Vashisht, M., Rani, P., Onteru, S. K., & Singh, D. (2017). Curcumin encapsulated in milk exosomes resists human digestion and possesses enhanced intestinal permeability in vitro. Applied Biochemistry and Biotechnology, 183(3), 993–1007. https://doi.org/10.1007/s12010-017-2478-4.

    Article  CAS  PubMed  Google Scholar 

  15. Saman, S., Kim, W. H., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A. C., Alvarez, V. E., Lee, N. C. Y., & Hall, G. F. (2012). Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. Journal of Biological Chemistry, 287(6), 3842–3849. https://doi.org/10.1074/jbc.M111.277061.

  16. Peinado, H., Alecˇković, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., et al. (2016). Corrigendum: melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Medicine, 22(12), 1502–1502. https://doi.org/10.1038/nm1216-1502b.

  17. Kim, M. S., Haney, M. J., Zhao, Y., Mahajan, V., Deygen, I., Klyachko, N. L., Inskoe, E., Piroyan, A., Sokolsky, M., Okolie, O., Hingtgen, S. D., Kabanov, A. V., & Batrakova, E. V. (2016). Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine: Nanotechnology, Biology, and Medicine, 12(3), 655–664. https://doi.org/10.1016/j.nano.2015.10.012.

    Article  CAS  Google Scholar 

  18. Tan, C., Lai, R., Wong, W., Dan, Y., Lim, S.-K., & Ho, H. (2014). Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Research & Therapy, 5(3), 76. https://doi.org/10.1186/scrt465.

    Article  CAS  Google Scholar 

  19. An, Q., Hückelhoven, R., Kogel, K. H., & van Bel, A. J. E. (2006). Multivesicular bodies participate in a cell wall-associated defence response in barley leaves attacked by the pathogenic powdery mildew fungus. Cellular Microbiology, 8(6), 1009–1019. https://doi.org/10.1111/j.1462-5822.2006.00683.x.

    Article  CAS  PubMed  Google Scholar 

  20. An, Q., van Bel, A. J., & Hückelhoven, R. (2007). Do plant cells secrete exosomes derived from multivesicular bodies? Plant Signaling & Behavior, 2(1), 4–7. https://doi.org/10.4161/psb.2.1.3596.

    Article  Google Scholar 

  21. Mu, J., Zhuang, X., Wang, Q., Jiang, H., Deng, Z. Bin, Wang, B., … Zhang, H. G. (2014). Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. Molecular Nutrition and Food Research, 58(7), 1561–1573. https://doi.org/10.1002/mnfr.201300729.

  22. Ju, S., Mu, J., Dokland, T., Zhuang, X., Wang, Q., Jiang, H., … Zhang, H.-G. (2013). Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Molecular Therapy, 21(7), 1345–1357. https://doi.org/10.1038/mt.2013.64.

  23. Mohan, A., Nair, S. V., & Lakshmanan, V. K. (2017). Leucas aspera nanomedicine shows superior toxicity and cell migration retarded in prostate cancer cells. Applied Biochemistry and Biotechnology, 181(4), 1388–1400. https://doi.org/10.1007/s12010-016-2291-5.

    Article  CAS  PubMed  Google Scholar 

  24. Singh, N., Verma, P., & Pandey, B. R. (2012). Therapeutic potential of organic Triticum aestivum Linn. (wheat grass) in prevention and treatment of chronic diseases: an overview. International Journal of Pharmaceutical Sciences and Drug Research, 4(1), 10–14 Retrieved from www.ijpsdr.com.

    CAS  Google Scholar 

  25. Ann Wigmore. (1985). The wheatgrass book. Avery.

  26. Chauhan, M. (2014). A pilot study on wheat grass juice for its phytochemical, nutritional and therapeutic potential on chronic diseases. International Journal of Chemical Studies, 2(4), 27–34.

    Google Scholar 

  27. Koçak, P., Canikyan, S., Batukan, M., Attar, R., Şahin, F., & Telci, D. (2016). Comparison of enzymatic and nonenzymatic isolation methods for endometrial stem cells. Turkish Journal of Biology, 40(5), 1081–1089. https://doi.org/10.3906/biy-1508-56.

    Article  CAS  Google Scholar 

  28. Reyes, A., Kazak, L., Wood, S. R., Yasukawa, T., Jacobs, H. T., & Holt, I. J. (2013). Mitochondrial DNA replication proceeds via a ‘bootlace’ mechanism involving the incorporation of processed transcripts. Nucleic Acids Research, 41(11), 5837–5850. https://doi.org/10.1093/nar/gkt196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang, Q., Zhuang, X., Mu, J., Deng, Z.-B., Jiang, H., Zhang, L., et al. (2013). Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids. Nature Communications, 4(May), 1867. https://doi.org/10.1038/ncomms2886.

  30. Ju, S., Mu, J., Dokland, T., Zhuang, X., Wang, Q., Jiang, H., et al. (2013). Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Molecular Therapy, 21(7), 1345–1357. https://doi.org/10.1038/mt.2013.64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang, B., Zhuang, X., Deng, Z.-B., Jiang, H., Mu, J., Wang, Q., Xiang, X., Guo, H., Zhang, L., Dryden, G., Yan, J., Miller, D., & Zhang, H.-G. (2014). Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Molecular Therapy, 22(3), 522–534. https://doi.org/10.1038/mt.2013.190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang, B., Zhuang, X., Deng, Z.-B., Jiang, H., Mu, J., Wang, Q., Xiang, X., Guo, H., Zhang, L., Dryden, G., Yan, J., Miller, D., & Zhang, H.-G. (2014). Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Molecular therapy : the journal of the American Society of Gene Therapy, 22(3), 522–534. https://doi.org/10.1038/mt.2013.190.

    Article  CAS  Google Scholar 

  33. Lauffenburger, D. A., & Horwitz, A. F. (1996). Cell migration: a physically integrated molecular process. Cell, 84(3), 359–369. https://doi.org/10.1016/S0092-8674(00)81280-5.

    Article  CAS  PubMed  Google Scholar 

  34. Martin, P., & Martin, P. (2016). Wound healing aiming for perfect skin. Regeneration, 276(5309), 75–81.

    Google Scholar 

  35. Weng, L., Brown, J., & Eng, C. (2001). PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways. Human molecular genetics., 10(3), 237–242. https://doi.org/10.1093/hmg/10.3.237.

    Article  CAS  PubMed  Google Scholar 

  36. Demirci, S., Doğan, A., Demirci, Y., & Şahin, F. (2014). In vitro wound healing activity of methanol extract of Verbascum speciosum. International Journal of Applied Research in Natural Products, 7(3), 37–44. https://doi.org/10.1155/2013/963457.

    Article  Google Scholar 

  37. Kim, M. R., Lee, H. S., Choi, H. S., Kim, S. Y., Park, Y., & Suh, H. J. (2014). Protective effects of ginseng leaf extract using enzymatic extraction against oxidative damage of UVA-irradiated human keratinocytes. Applied Biochemistry and Biotechnology, 173(4), 933–945. https://doi.org/10.1007/s12010-014-0886-2.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Dr. Pakize Neslihan Taşlı for her help.

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Correspondence to Fikrettin Şahin.

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Şahin, F., Koçak, P., Güneş, M.Y. et al. In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles. Appl Biochem Biotechnol 188, 381–394 (2019). https://doi.org/10.1007/s12010-018-2913-1

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