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Adipose-Derived Stem Cell Coculturing Stimulates Integrin-Mediated Extracellular Matrix Adhesion of Melanocytes by Upregulating Growth Factors

  • Kim, Hyangmi (Department of Dermatology, Dongguk University Ilsan Hospital) ;
  • Yi, Nayoung (Department of Dermatology, Dongguk University Ilsan Hospital) ;
  • Do, Byung-Rok (Biotechnology Research Institute, Hurim BioCell Inc.) ;
  • Lee, Ai-Young (Department of Dermatology, Dongguk University Ilsan Hospital)
  • Received : 2018.10.23
  • Accepted : 2018.11.15
  • Published : 2019.03.01

Abstract

Coculture with adipose-derived stem cells (ADSCs) can stimulate proliferation and migration of melanocytes. To enhance outcomes of skin disorders caused by melanocyte loss or death, mixed transplantation with ADSCs has been suggested. However, role of cocultured ADSCs in proliferation and migration of melanocytes remains unclear. This study determined the effect of ADSCs on production of growth factors and expression levels of intergrins in primary culture of adult human melanocytes with or without ADSCs and in nude mice grafted with such melanocytes. Higher amounts of growth factors for melanocytes, such as bFGF and SCF were produced and released from ADSCs by coculturing with melanocytes. Relative levels of integrins ${\beta}1$, ${\alpha}5$, and ${\alpha}6$ as well as adhesion to fibronectin and laminin were increased in melanocytes cocultured with ADSCs. Such increases were inhibited by neutralization of bFGF or SCF. Relative levels of bFGF, SCF and integrins were increased in nude mice skin after grafting with melanocyte+ADSC cocultures. Collectively, these results indicate that ADSCs can stimulate proliferation and migration of melanocytes by increasing expression of integrins in melanocytes through upregulation of production/release of melanocyte growth factors such as bFGF and SCF.

Keywords

References

  1. Ahn, H. H., Lee, I. W., Lee, H. B. and Kim, M. S. (2014) Cellular behavior of human adipose-derived stem cells on wettable gradient polyethylene surfaces. Int. J. Mol. Sci. 15, 2075-2086. https://doi.org/10.3390/ijms15022075
  2. Akiyama, S. K. (1996) Integrins in cell adhesion and signaling. Hum. Cell 9, 181-186.
  3. Bin, B. H., Kim, D. K., Kim, N. H., Choi, E. J., Bhin, J., Kim, S. T., Gho, Y. S., Lee, A. Y., Lee, T. R. and Cho, E. G. (2016) Fibronectin-containing extracellular vesicles protect melanocytes against ultraviolet radiation-induced cytotoxicity. J. Invest. Dermatol. 136, 957-966. https://doi.org/10.1016/j.jid.2015.08.001
  4. Giancotti, F. G. and Tarone, G. (2003) Positional control of cell fate through joint integrin/receptor protein kinase signaling. Annu. Rev. Cell Dev. Biol. 19, 173-206. https://doi.org/10.1146/annurev.cellbio.19.031103.133334
  5. Halaban, R., Fan, B., Ahn, J., Funasaka, Y., Gitay-Goren, H. and Neufeld, G. (1992) Growth factors, receptor kinases, and protein tyrosine phosphatases in normal and malignant melanocytes. J. Immunother. 12, 154-161. https://doi.org/10.1097/00002371-199210000-00002
  6. Hara, M., Yaar, M., Tang, A., Eller, M. S., Reenstra, W. and Gilchrest, B. A. (1994) Role of integrins in melanocyte attachment and dendricity. J. Cell Sci. 107, 2739-2748. https://doi.org/10.1242/jcs.107.10.2739
  7. Hirobe, T. (2005) Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes. Pigment Cell Res. 18, 2-12. https://doi.org/10.1111/j.1600-0749.2004.00198.x
  8. Hong, S. J., Traktuev, D. O. and March, K. L. (2010) Therapeutic potential of adipose-derived stem cells in vascular growth and tissue repair. Curr. Opin. Organ. Transplant. 15, 86-91. https://doi.org/10.1097/MOT.0b013e328334f074
  9. Jimbow, K., Roth, S. I., Fitzpatrick, T. B. and Szabo, G. (1975) Mitotic activity in non-neoplastic melanocytes in vivo as determined by histochemical, autoradiographic, and electron microscope studies. J. Cell Biol. 66, 663-670. https://doi.org/10.1083/jcb.66.3.663
  10. Kim, J. Y., Park, C. D., Lee, J. H., Lee, C. H., Do, B. R. and Lee, A. Y. (2012) Co-culture of melanocytes with adipose-derived stem cells as a potential substitute for co-culture with keratinocytes. Acta Derm. Venereol. 92, 16-23. https://doi.org/10.2340/00015555-1174
  11. Kumar, R., Parsad, D. and Kanwar, A. J. (2011) Role of apoptosis and melanocytorrhagy: a comparative study of melanocyte adhesion in stable and unstablevitiligo. Br. J. Dermatol. 164, 187-191. https://doi.org/10.1111/j.1365-2133.2010.10039.x
  12. Lee, A. Y., Kim, N. H., Choi, W. I. and Youm, Y. H. (2005) Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J. Invest. Dermatol. 124, 976-983. https://doi.org/10.1111/j.0022-202X.2005.23667.x
  13. Lim, W. S., Kim, C. H., Kim, J. Y., Do, B. R., Kim, E. J. and Lee, A. Y. (2014) Adipose-derived stem cells improve efficacy of melanocyte transplantation in animal skin. Biomol. Ther. (Seoul) 22, 328-333. https://doi.org/10.4062/biomolther.2014.065
  14. Liu, J., Wang, H., Wang, Y., Yin, Y., Wang, L., Liu, Z., Yang, J., Chen, Y. and Wang, C. (2014) Exendin-4 pretreated adipose derived stem cells are resistant to oxidative stress and improve cardiac performance via enhanced adhesion in the infarcted heart. PLoS ONE 9, e99756. https://doi.org/10.1371/journal.pone.0099756
  15. Olsson, M. J. and Juhlin, L. (2002) Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br. J. Dermatol. 147, 893-904. https://doi.org/10.1046/j.1365-2133.2002.04837.x
  16. Pawelek, J. M. (1979) Evidence suggesting that a cyclic AMP-dependent protein kinase is a positive regulator of proliferation in Cloudman S91 melanoma cells. J. Cell Physiol. 98, 619-625. https://doi.org/10.1002/jcp.1040980320
  17. Pinon, P. and Wehrle-Haller, B. (2011) Integrins: versatile receptors controlling melanocyte adhesion, migration and proliferation. Pigment Cell Melanoma Res. 24, 282-294. https://doi.org/10.1111/j.1755-148X.2010.00806.x
  18. Ricard, A. S., Pain, C., Daubos, A., Ezzedine, K., Lamrissi-Garcia, I., Bibeyran, A., Guyonnet-Duperat, V., Taieb, A. and Cario-Andre, M. (2012) Study of CCN3 (NOV) and DDR1 in normal melanocytes and vitiligo skin. Exp. Dermatol. 21, 411-416. https://doi.org/10.1111/j.1600-0625.2012.01473.x
  19. Scott, G., Ewing, J., Ryan, D. and Abboud, C. (1994) Stem cell factor regulates human melanocyte-matrix interactions. Pigment Cell Res. 7, 44-51. https://doi.org/10.1111/j.1600-0749.1994.tb00017.x
  20. Scott, G., Cassidy, L. and Busacco, A. (1997) Fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent mechanism. J. Invest. Dermatol. 108, 147-153. https://doi.org/10.1111/1523-1747.ep12332650
  21. Shingyochi, Y., Orbay, H. and Mizuno, H. (2015) Adipose-derived stem cells for wound repair and regeneration. Expert Opin. Biol. Ther. 15, 1285-1292. https://doi.org/10.1517/14712598.2015.1053867
  22. Sviderskaya, E. V., Wakeling, W. F. and Bennett, D. C. (1995) A cloned, immortal line of murine melanoblasts inducible to differentiate to melanocytes. Development 121, 1547-1557. https://doi.org/10.1242/dev.121.5.1547
  23. Zambruno, G., Marchisio, P. C., Melchiori, A., Bondanza, S., Cancedda, R., De Luca, M. (1993) Expression of integrin receptors and their role in adhesion, spreading and migration of normal human melanocytes. J. Cell Sci. 105, 179-190. https://doi.org/10.1242/jcs.105.1.179
  24. Zhang, R., Premi, S., Kilic, S. S., Bacchiocchi. A., Halaban, R. and Brash, D. E. (2013) Clonal growth of human melanocytes using cell-free extracellular matrix. Pigment Cell Melanoma Res. 26, 925-927. https://doi.org/10.1111/pcmr.12159
  25. Zuk, P. A., Zhu, M., Ashjian, P., De Ugarte, D. A., Huang, J. I., Mizuno, H., Alfonso, Z. C., Fraser, J. K., Benhaim, P. and Hedrick, M. H. (2002) Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279-4295. https://doi.org/10.1091/mbc.e02-02-0105

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