Skip to main content
SpringerLink
Log in

Specific Activity of Electron-Beam Synthesis Immobilized Hyaluronidase on G-CSF Induced Mobilization of Bone Marrow Progenitor Cells

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

The effects of nanotechnology (electron-beam) –PEGylated (or immobilized; Im) hyaluronidase (HD) on the state of the pool of bone marrow progenitor cells and their mobilization induced by granulocyte colony stimulating factor (G-CSF) were studied. A high specific activity of the drug Im-HD on progenitor cells of different classes was demonstrated using parenteral and enteral administration. An increase in the content of erythroid (E), granulomonocytic (GM), fibroblast (F) colony-forming units (CFU) and mesenchymal stem cells (MSC) in bone marrow was shown, as well as G-CSF-induced stimulation of mobilization of precursors into the peripheral blood under the influence of Im-HD. The detected activity of this novel drug on progenitor cells indicates the potential for a safe and highly effective treatment for hematology practice and regenerative medicine.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Goldberg, E. D., Dygai, A. M., & Zhdanov, V. V. (1999). The role of the microenvironment, inducing hematopoiesis during cytostatic myelosuppression (p. 114). Tomsk: STT.

    Google Scholar 

  2. Goldberg, E. D., Dygai, A. M., & Zyuzkov, G. N. (2006). Hypoxia and the blood system (p. 142). Tomsk: Tomsk Univ.

    Google Scholar 

  3. Avigdor, A., Goichberg, P., Shivtiel, S., Dar, A., Peled, A., Samira, S., Kollet, O., Hershkoviz, R., Alon, R., Hardan, I., Ben-Hur, H., Naor, D., Nagler, A., & Lapidot, T. (2004). CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood, 103(8), 2981–2989.

    Article  PubMed  CAS  Google Scholar 

  4. Dygai, A. M., & Zyuzkov, G. N. (2009). Cellular therapy: new points of view. Science in Russia, Moscow. Science, 169(1), 4–8.

    Google Scholar 

  5. Goldberg, E. D., Dygai, A. M., Zhdanov, V. V., Vetoshkina, T. V., Guryantseva, L. A., Dubskaya, T. Y., Ermolaeva, L. A., Zyuzkov, G. N., Simanina, E. V., Sotnikova, N. V., Stavrova, L. A., Udut, E. V., Fomina, T. I., & Khrichkova, T. Y. (2007). Creation of experimental models and study of the regeneratory potential of stem cells on these models. Bulletin of Experimental Biology and Medicine, 143(1 suppl), 1–8.

    Article  Google Scholar 

  6. Dygai, A. M., Zyuz’kov, G. N., Zhdanov, V. V., Madonov, P. G., Udut, E. V., Miroshnichenko, L. A., Khrichkova, T. Y., Simanina, E. V., Stavrova, L. A., Artamonov, A. V., et al. (2011). Pharmacological properties of granulocytic colony-stimulating factor Pegylated using electron beam synthesis nanotechnologies. Bulletin of Experimental Biology and Medicine, 152(1), 133–137.

    Article  PubMed  CAS  Google Scholar 

  7. Draper, J. S., Smith, K., Gokhale, P., Moore, H. D., Maltby, E., Johnson, J., Meisner, L., Zwaka, T. P., Thomson, J. A., & Andrews, P. W. (2004). Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nature Biotechnology, 22, 53–54.

    Article  PubMed  CAS  Google Scholar 

  8. Zyuz’kov, G. N., Suslov, N. I., Dygai, A. M., Zhdanov, V. V., & Goldberg, E. D. (2005). Role of stem cells in adaptation to hypoxia and mechanisms of neuroprotective effect of granulocytic colony-stimulating factor. Bulletin of Experimental Biology and Medicine, 140(5), 606–611.

    Article  PubMed  Google Scholar 

  9. Epshtein, O. I., Zyuz’kov, G. N., Sotnikova, N. V., Stavrova, L. A., Fomina, T. I., Vetoshkina, T. V., Sergeeva, S. A., Dubskaya, T. Y., Dygai, A. M., & Goldberg, E. D. (2005). Mechanisms of hepatoprotective effect of preparation containing superlow doses of antibodies to granulocytic colony-stimulating factor. Bulletin of Experimental Biology and Medicine, 140(5), 598–602.

    Article  Google Scholar 

  10. Stavrova, L. A., Fomina, T. I., Plotnikov, M. B., Aliev, O. I., Sotnikova, N. V., Epshtein, O. I., Sergeeva, S. A., Guryantseva, L. A., Zyuz’kov, G. N., Zhdanov, V. V., Dygai, A. M., & Goldberg, E. D. (2005). Pharmacological regulation of functional activity of stem cells in restoration of the myocardium during the postinfarction period. Bulletin of Experimental Biology and Medicine, 140(5), 593–597.

    Article  PubMed  CAS  Google Scholar 

  11. Goldberg, E. D., Dygai, A. M., & Zyuz’kov, G. N. (2006). Mechanisms of regulation of blood system during oxygen deficiency and the participation of neural stem cells in adaptation to hypoxia. Bull Siberian Med, 2, 43–51.

    Google Scholar 

  12. Goldberg, E. D., Dygai, A. M., Zhdanov, V. V., Zyuz’kov, G. N., Ermakova, N. N., Vetoshkina, T. V., Fomina, T. I., Ermolaeva, L. A., & Dubskaya, T. Y. (2007). Mechanisms of therapeutic effects of granulocytic colony-stimulating factor in experimental diabetes mellitus. Bulletin of Experimental Biology and Medicine, 146(4), 543–546.

    Article  Google Scholar 

  13. Ermakova, N. N., Zhdanov, V. V., Dygai, A. M., Zyuz’kov, G. N., Stavrova, L. A., Guryantseva, L. A., Khrichkova, T. Y., Udut, E. V., Vetoshkina, T. V., Fomina, T. I., Ermolaeva, L. A., & Goldberg, E. D. (2009). Mechanisms underlying the effects of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of damaged Pan-creatic tissue in experimental diabetes mellitus. Bulletin of Experimental Biology and Medicine, 148(3), 549–552.

    Article  PubMed  CAS  Google Scholar 

  14. Zyuz’kov, G. N., Zhdanov, V. V., Guryantseva, L. A., Stavrova, L. A., Khrichkova, T. Y., Dygai, A. M., & Goldberg, E. D. (2009). Role of mesenchymal precursor cells in the stimulation of wound healing under the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor. Bulletin of Experimental Biology and Medicine, 148(3), 553–555.

    Article  PubMed  Google Scholar 

  15. Stavrova, L.A., Zyuźkov, G.N., Simanina, E.V., Miroshnichenko, L.A., Udut, E.V., Khrichkova, T.Y., Skurikhin, E.G., Pershina, O.V., Ermakova, N.N., Firsova, T.V., Zhdanov, V.V., Dygai, A.M., & Goldberg, E.D. (2009). Hemostimualting properties of preparation containing ultralow doses of antibodies to stem cell factor in cytostatic myelosuppression. Bulletin of Experimental Biology and Medicine, 148(3), 556–559.

    Google Scholar 

  16. Zhu, H., Mitsuhashi, N., Klein, A., Barsky, L. W., Weinberg, K., Barr, M. L., Demetriou, A., & Wu, G. D. (2006). The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells, 24(4), 928–935.

    Article  PubMed  CAS  Google Scholar 

  17. Nedvetzki, S., Gonen, E., Assayag, N., Reich, R., Williams, R. O., Thurmond, R. L., Huang, J. F., Neudecker, B. A., Wang, F. S., Turley, E. A., & Naor, D. (2004). RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: a different interpretation of redundancy. Proceedings of the National Academy of Sciences USA, 101(52), 18081–18086.

    Article  CAS  Google Scholar 

  18. Stern, R. (2003). Devising a pathway for hyaluronan catabolism: are we there yet? Glycobiology, 13(12), 105–115.

    Article  Google Scholar 

  19. Noble, P. W. (2002). Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biology, 21, 25–29.

    Article  PubMed  CAS  Google Scholar 

  20. Goldberg, E. D., Dygai, A. M., Zyuz’kov, G. N., Zhdanov, V. V., Simanina, E. V., & Guryantseva, L. A. (2007). Role of hyaluronidase in the regulation of functions of mesenchymal precursor cells. Bulletin of Experimental Biology and Medicine, 143(4), 548–551.

    Article  PubMed  CAS  Google Scholar 

  21. Goldberg, E. D., Dygai, A. M., Zyuz’kov, G. N., & Zhdanov, V. V. (2007). Mechanisms of mobilization of mesenchymal precursor cell under the effect of granulocytic colony-stimulating factor and hyaluronidase. Bulletin of Experimental Biology and Medicine, 144(6), 802–805.

    Article  PubMed  CAS  Google Scholar 

  22. Goldberg, E. D., Dygai, A. M., Zyuz’kov, G. N., Zhdanov, V. V., Simanina, E. V., & Guryantseva, L. A. (2007). Role of hyaluronidase in the regulation of hemopoiesis. Bulletin of Experimental Biology and Medicine, 144(6), 840–845.

    Article  Google Scholar 

  23. Zyuz’kov, G. N., Zhdanov, V. V., Dygai, A. M., & Goldberg, E. D. (2007). Role of hyaluronidase in the regulation of hematopoiesis. Bulletin of Experimental Biology and Medicine, 12, 690–695.

    Google Scholar 

  24. Goldberg, E. D., Dygai, A. M., Zyuz’kov, G. N., & Zhdanov, V. V. (2008). Effects of granulocyte colony-stimulating factor and hyaluronidase on the formation of blood system reactions. Bulletin of Experimental Biology and Medicine, 145(6), 682–687.

    Article  PubMed  CAS  Google Scholar 

  25. Vereschagin, E. I., Han, D. H., Troitsky, A. W., Grishin, O. V., Petrov, S. E., Gulyaeva, E. P., Bogdanova, L. A., Korobeinikov, M. V., & Auslender, V. L. (2001). Radiation technology in the preparation of polyethylene oxide hydrophilic gels and immobilization of proteases for use in medical practice. Archives of Pharmacal Research, 24(3), 229–233.

    Article  PubMed  CAS  Google Scholar 

  26. Dygai, A. M., Vereschagin, E. I., Zyuz’kov, G. N., Zhdanov, V. V., Madonov, P. G., Simanina, E. V., Stavrova, L. A., Udut, E. V., Khrichkova, T. Y., Miroshnichenko, L. A., Minakova, M. Y., Ermakova, N. N., Firsova, T. V., Dygai, A. M., Vereshchagin, E. I., Zyuz’kov, G. N., Zhdanov, V. V., & Madonov, P. G. (2009). Mobilization of progenitor cells into the blood by immobilized granulocytic colony-stimulating factor. Bulletin of Experimental Biology and Medicine, 147(4), 499–502.

    Article  PubMed  CAS  Google Scholar 

  27. Andreeva, T. V., & Zyuzkov, G. N. (2009). Hemostimulating activity of the immobilized granulocyte colony-stimulating factor. Siberian Journal Cancer, 1(suppl), 15–16.

    Google Scholar 

  28. Sharaev, P. N., Strelkov, N. S., Shklayeva, E. V., et al. (1996). The determination of hyluronidase activity. Clinical Laboratory Diagnostics, 3, 21–22.

    Google Scholar 

  29. Goldberg, E. D., Dygai, A. M., & Schachov, V. P. (1992). Methods of tissue culture in hematology (p. 272). Tomsk: Tomsk Univ.

    Google Scholar 

  30. in’t Anker, P. S., Noort, W. A., Scherjon, S. A., Kleijburg-van der Keur, C., Kruisselbrink, A. B., van Bezooijen, R. L., Beekhuizen, W., Willemze, R., Kanhai, H. H., & Fibbe, W. E. (2003). Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogenous multilineage differentiation potential. Haematologica, 88, 845–852.

    Google Scholar 

  31. Glanz, S. (1998). Medico-biological statistics. Moscow “Practice”, pp. 459

  32. Bonnefoix, T., Bonnefoix, P., Callanan, M., Verdiel, P., & Sotto, J. J. (2001). Graphical representation of a generalized linear model-based statistical test estimating the fit of the single-hit poisson model to limiting dilution assays. Journal of Immunology, 167, 5725–5730.

    CAS  Google Scholar 

  33. Seyfulla, R. D., Timofeev, A. B., Ordzhonikidze, Z. G., Rozhkova, E. A., Kulikova, E. V., Druzhinin, A. E., Kuznetsov, Y. M., & Kim, E. K. (2008). Problems of using nanotechnology in pharmacology. Experimental and Clinical Pharmacology, 71(1), 61–69.

    Google Scholar 

  34. Piedmonte, D. M., & Treuheit, M. J. (2008). Formulation of Neulasta (pegfilgrastim). Advanced Drug Delivery Reviews, 60, 50–58.

    Article  PubMed  CAS  Google Scholar 

  35. Dygai, A. M., Zyuzkov, G. N., Zhdanov, V. V., Simanina, E. V., Stavrova, L. A., Udut, E. V., Khrichkova, T. Y., Minakova, M. Y., Ermakova, N. N., & Firsova, T. V. (2009). Effect of transplantation of peripheral blood mononuclears obtained using granulocytic colony-stimulating factor and Hyaluronidase on regeneration of hemopoietic tissue during myelosuppression. Bulletin of Experimental Biology and Medicine, 148(1), 120–125.

    Article  PubMed  CAS  Google Scholar 

  36. Bruns, I., Steidl, U., Fischer, J. C., Czibere, A., Kobbe, G., Raschke, S., Singh, R., Fenk, R., Rosskopf, M., Pechtel, S., von Haeseler, A., Wernet, P., Tenen, D. G., Haas, R., & Kronenwett, R. (2008). Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor. Haematologica, 93, 347–355.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of Interest

The authors indicate no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Federal State Budgetary Institution, “Research Institute of Pharmacology” under the Siberian Branch of Russian Academy of Medical Sciences, Tomsk city (director - academician of RAMS A.M. Dygai), 634028, Tomsk, Lenin Avenue, 3 (Institute of Pharmacology of RAMS SB), Russia

    A. M. Dygai, G. N. Zyuz’kov, V. V. Zhdanov, E. V. Udut, L. A. Miroshnichenko, E. V. Simanina, T. Yu. Khrichkova, M. Yu. Minakova & P. G. Madonov

Authors
  1. A. M. Dygai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. N. Zyuz’kov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. V. Zhdanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. V. Udut
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. A. Miroshnichenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. V. Simanina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Yu. Khrichkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Yu. Minakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. G. Madonov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Yu. Minakova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dygai, A.M., Zyuz’kov, G.N., Zhdanov, V.V. et al. Specific Activity of Electron-Beam Synthesis Immobilized Hyaluronidase on G-CSF Induced Mobilization of Bone Marrow Progenitor Cells. Stem Cell Rev and Rep 9, 140–147 (2013). https://doi.org/10.1007/s12015-012-9423-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-012-9423-2

Keywords

Search

Navigation