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The Problem of Terminal Differentiation and Apoptosis during Human Keratinocytes’ Cryostorage in Suspension

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Abstract

Cryostorage of human epidermal keratinocytes is an essential stage in living epidermal equivalent’s manufacturing. However, cryostorage of keratinocytes in suspension stimulates processes of terminal differentiation and apotosis leading to massive loss of stem and progenitor keratinocytes. Suspension-induced signal of disruption between β1 integrin and extracellular matrix causes simultaneous activation of PI3K/Akt- and Caspase-8 pathways. It is assumed that terminal differentiation could be blocked by fibronectin, PI3-kinase, and Caspase-8-inhibitors added to culture medium after cryostorage in suspension.

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REFERENCES

  1. Adams, J.C. and Watt, F.M., Fibronectin inhibits the terminal differentiation of human keratinocytes, Nature, 1989, vol. 340, no. 6231, pp. 307–309.

    Article  CAS  Google Scholar 

  2. Adams, J.C. and Watt, F.M., Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedes alpha 5 beta 1 integrin loss from the cell surface, Cell, 1990, vol. 63, no. 2, pp. 425–435.

    Article  CAS  Google Scholar 

  3. Averill-Bates, D.A., Yée, M.C.-S., Grondin, M., et al., Cryopreservation of rat hepatocytes with wheat proteins: role in oxidative stress protection, Cryobiology, 2014, vol. 69, no. 3, pp. 512–513.

    Article  Google Scholar 

  4. Bagutti, C., Wobus, A.M., Fassler, R., et al., Differentiation of embryonal stem cells into keratinocytes: comparison of wild-type and beta 1 integrin-deficient cells, Dev. Biol., 1996, vol. 179, no. 1, pp. 184–196.

    Article  CAS  Google Scholar 

  5. Borderie, V.M., Lopez, M., Lombet, A., et al., Cryopreservation and culture of human corneal keratocytes, Invest. Ophthalmol. Vis. Sci., 1998, vol. 39, no. 8, pp. 1511–1519.

    CAS  PubMed  Google Scholar 

  6. Danilkovitch-Miagkova, A., Angeloni, D., Skeel, A., et al., Integrin-mediated RON growth factor receptor phosphorylation requires tyrosine kinase activity of both the receptor and c-Src, J. Biol. Chem., 2000, vol. 275, no. 20, pp. 14783–14786.

    Article  CAS  Google Scholar 

  7. Darribere, T., Guida, K., Larjava, H., et al., In vivo analyses of integrin beta 1 subunit function in fibronectin matrix assembly, J. Cell Biol., 1990, vol. 110, no. 5, pp. 1813–1823.

    Article  CAS  Google Scholar 

  8. Evans, R.D., Perkins, V.C., Henry, A., et al., A tumor-associated beta 1 integrin mutation that abrogates epithelial differentiation control, J. Cell Biol., 2003, vol. 160, no. 4, pp. 589–596.

    Article  CAS  Google Scholar 

  9. Grassian, A.R., Schafer, Z.T., and Brugge, J.S., ErbB2 stabilizes epidermal growth factor receptor (EGFR) expression via Erk and Sprouty2 in extracellular matrix-detached cells, J. Biol. Chem., 2011, vol. 286, no. 1, pp. 79–90.

    Article  CAS  Google Scholar 

  10. Haase, I., Hobbs, R.M., Romero, M.R., et al., A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis, J. Clin. Invest., 2001, vol. 108, pp. 527–536.

    Article  CAS  Google Scholar 

  11. Hanahan, D. and Weinberg, R.A., The hallmarks of cancer, Cell, 2000, vol. 100, no. 1, pp. 57–70.

    Article  CAS  Google Scholar 

  12. Heng, B.C., Ye, C.P., Liu, H., Toh, W.S., et al., Loss of viability during freeze-thaw of intact and adherent human embryonic stem cells with conventional slow-cooling protocols is predominantly due to apoptosis rather than cellular necrosis, J. Biomed. Sci., 2006, vol. 13, no. 3, pp. 433–445.

    Article  CAS  Google Scholar 

  13. Hertle, M.D., Adams, J.C., and Watt, F.M., Integrin expression during human epidermal development in vivo and in vitro, Development, 1991, vol. 112, no. 1, pp. 193–206.

    Article  CAS  Google Scholar 

  14. Jackson, C., Aabel, P., Eidet, J.R., et al., Effect of storage temperature on cultured epidermal cell sheets stored in xenobiotic-free medium, PLoS One, 2014, vol. 9, no. 8, р. e105808.

  15. Janes, S.M., Ofstad, T.A., Campbell, D.H., et al., PI3-kinase-dependent activation of apoptotic machinery occurs on commitment of epidermal keratinocytes to terminal differentiation, Cell Res., 2009, vol. 19, no. 3, pp. 328–339.

    Article  CAS  Google Scholar 

  16. Levy, L., Broad, S., Diekmann, D., et al., b1 integrins regulate keratinocyte adhesion and differentiationby distinct mechanisms, Cell, 2000, vol. 11, pp. 453–466.

    CAS  Google Scholar 

  17. De Luca, M., Pellegrini, G., and Green, H., Regeneration of squamous epithelia from stem cells of cultured grafts, Regen. Med., 2006, vol. 1, pp. 45–57.

    Article  CAS  Google Scholar 

  18. Meryman, H.T., Cryopreservation of living cells: principles and practice, Transfusion, 2007, vol. 47, no. 5, pp. 935–945.

    Article  CAS  Google Scholar 

  19. Metral, E., Bechetoille, N., Demarne, F., et al., α6 integrin (α6high)/transferrin receptor (CD71) low keratinocyte stem cells are more potent for generating reconstructed skin epidermis than rapid adherent cells, Int. J. Mol. Sci, 2017, vol. 18, no. 2, р. е282.

  20. Miranti, C. and Brugge, J., Sensing the environment: a historical perspective on integrin signal transduction, Nat. Cell Biol., 2002, vol. 4, no. 4, pp. e83–e90.

    Article  CAS  Google Scholar 

  21. Mitra, R.S., Wrone-Smith, T., Simonian, P., et al., Apoptosis in keratinocytes is not dependent on induction of differentiation, Lab. Invest., 1997, vol. 76, no. 1, pp. 99–107.

    CAS  PubMed  Google Scholar 

  22. Moro, L., Venturino, M., Bozzo, C., et al., Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival, EMBO J., 1998, vol. 17, no. 22, pp. 6622–6632.

    Article  CAS  Google Scholar 

  23. Muller, P., Aurich, H., Wenkel, R., et al., Serum-free cryopreservation of porcine hepatocytes, Cell Tiss. Res., 2004, vol. 317, no. 1, pp. 45–56.

    Article  Google Scholar 

  24. Naaldijk, Y., Friedrich-Stöckigt, A., Sethe, S., et al., Comparison of different cooling rates for fibroblast and keratinocyte cryopreservation, J. Tiss. Eng. Regen. Med., 2016, vol. 10, no. 10, pp. e354–e364.

    Article  CAS  Google Scholar 

  25. Pasch, J., Schiefer, A., Heschel, I., et al., Variation of the HES concentration for the cryopreservation of keratinocytes in suspensions and in monolayers, Cryobiology, 2000, vol. 41, no. 2, pp. 89–96.

    Article  CAS  Google Scholar 

  26. Rama, P., et al., Limbal stem-cell therapy and long-term corneal regeneration, N. Engl. J. Med., 2010, vol. 363, pp. 147–155.

    Article  CAS  Google Scholar 

  27. Rao, B.S., Mahesh, Y.U., Charan, K.V., et al., Effect of vitrification on meiotic maturation and expression of genes in immature goat cumulus oocyte complexes, Cryobiology, 2012, vol. 64, no. 3, pp. 176–184.

    Article  CAS  Google Scholar 

  28. Reginato, J., Mills, K.R., Paulus, J.K., et al., Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis, Nat. Cell Biol., 2003, vol. 5, no. 8, pp. 733–740.

    Article  CAS  Google Scholar 

  29. Rippa, A.L., Vorotelyak, E.A., Vasiliev, A.V., et al., The role of integrins in the development and homeostasis of the epidermis and skin appendages, Acta Naturae, 2013, vol. 5, no. 4, pp. 22–33.

    Article  CAS  Google Scholar 

  30. Soldi, R., Mitola, S., Strasly, M., et al., Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2, EMBO J., 1999, vol. 18, no. 4, pp. 882–892.

    Article  CAS  Google Scholar 

  31. Stupack, D.G., Puente, X.S., Boutsaboualoy, S., et al., Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins, J. Cell Biol., 2001, vol. 155, no. 3, pp. 459–470.

    Article  CAS  Google Scholar 

  32. Terskikh, V.V. and Vasiliev, A.V., Apoptosis and differentiation of epidermal keratinocytes, Russ. J. Dev. Biol., 2005, vol. 36, pp. 61–64.

    Article  Google Scholar 

  33. Tiberio, R., Marconi, A., Fila, C., et al., Keratinocytes enriched for stem cells are protected from anoikis via an integrin signaling pathway in a Bcl-2 dependent manner, FEBS Lett., 2002, vol. 524, nos. 1–3, pp. 139–144.

    Article  CAS  Google Scholar 

  34. Watt, F.M., Role of integrins in regulating epidermal adhesion, growth and differentiation, EMBO J., 2002, vol. 21, no. 15, pp. 3919–3926.

    Article  CAS  Google Scholar 

  35. Watt, F., Kubler, M.D., Hotchin, N.A., et al., Regulation of keratinocyte terminal differentiation by integrin-extracellular matrix interactions, J. Cell Sci., 1993, vol. 106, pp. 175–182.

    Article  Google Scholar 

  36. Woelders, H. and Chaveiro, A., Theoretical prediction of optimal freezing programmes, Cryobiology, 2004, vol. 49, pp. 258–271.

    Article  CAS  Google Scholar 

  37. Xiao, M. and Dooley, D.C., Assessment of cell viability and apoptosis in human umbilical cord blood following storage, J. Hematother. Stem Cell Res., 2003, vol. 12, no. 1, pp. 115–122.

    Article  CAS  Google Scholar 

  38. Zhu, A.J., Haase, I., and Watt, F.M., Signaling via b1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro, Proc. Nat. Acad. Sci. U. S. A., 1999, vol. 96, pp. 6728–6733.

    Article  CAS  Google Scholar 

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Funding

This work was supported by the Russian Science Foundation (project no. 21-74-30015).

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Correspondence to A. N. Popova or E. A. Vorotelyak.

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The authors declare that they have no conflict of interests.

This article does not contain a description of the research carried out by the authors with the participation of humans or the use of animals as objects.

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Popova, A.N., Vorotelyak, E.A. The Problem of Terminal Differentiation and Apoptosis during Human Keratinocytes’ Cryostorage in Suspension. Russ J Dev Biol 52, 215–219 (2021). https://doi.org/10.1134/S1062360421040068

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  • DOI: https://doi.org/10.1134/S1062360421040068

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