Medical and Biological Engineering and Computing

, Volume 36, Issue 6, pp 821–824 | Cite as

Reconstructed human epidermis composed of keratinocytes, melanocytes and Langerhans cells

  • M. Régnier
  • A. Patwardhan
  • A. Scheynius
  • R. Schmidt
Cellular Engineering: Bioengineering of the Skin


In addition to their basic biological interest, models of reconstructed epidermis provide useful tools for in vitro assessment of the toxicology and efficacy of new chemicals and drugs. The fact that the majority of these in vitro models are composed only of keratinocytes has excluded their use in the fields of skin pigmentation and immunology. After the successful introduction of functional melanocytes into the epidermal reconstruct, the integration of Langerhans cells remains an important challenge, particularly since after isolation of Langerhans cells from human epidermis, these cells cannot be subcultured and do not integrate into the reconstructing epidermis. The authors show that cord blood derived and CD34+ progenitors isolated from the peripheral blood give rise to residential Langerhans cells when co-seeded with normal human keratinocytes.


Reconstructed epidermis Langerhans cells Melanocytes 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bessou, S., Surléve-Bazeille, J. E., Sorbier, E., andTaïb, A. (1995): ‘Ex vivo reconstruction of the epidermis with melanocytes and the influence of UVB’,Pigment Cell Res., pp. 241–249Google Scholar
  2. Caux, C., Dezutter-Dambuyant, C., Schmidt, D., andBanchereau, J. (1992): ‘GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells’,Nature,360, pp. 258–261CrossRefGoogle Scholar
  3. Caux, C., Vanbervliet, B., Massacrier, C., Dezutter-Dambuyant, C., de Saint-Vis, B., Jacquet, C., Yoneda, K., Imamura, S., Schmidt, D., andBanchereau, J. (1996): ‘CD34+ haematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF-α’,J. Exp. Med.,184, pp. 695–706CrossRefGoogle Scholar
  4. Haake, A. R., andScott, G. A. (1991): ‘Physiologic distribution and differentiation of melanocytes in human fetal and neonatal skin equivalents’,J. Invest. Dermatol.,96, pp. 71–77CrossRefGoogle Scholar
  5. Kashihara, M., Ueda, M., Horiguchi, Y., Furukawa, F., Hanaoka, M., andImamura, S. (1986): ‘A monoclonal antibody specifically reactive to human Langerhans cells’,J. Invest. Dermatol.,87, pp. 602–607CrossRefGoogle Scholar
  6. Katz, S. I., Tamaki, K., andSachs, D. H. (1979): ‘Epidermal Langerhans cells are derived from cells originating in bone marrow’,Nature,282, pp. 324–326CrossRefGoogle Scholar
  7. Kripke, M. L., Munn, C. G., Jeevan, A., Tang, J. M., andBucana, C. (1990): ‘Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitisation’,J. Immunol.,145, pp. 2833–2838Google Scholar
  8. Lukas, M., Stössel, H., Hefel, L., Imamura, S., Fritsch, P., Sepp, N. T., Schuler, G., andRomani, N. (1996): ‘Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a skin organ culture model’,J. Invest. Dermatol.,106, pp. 1293–1299CrossRefGoogle Scholar
  9. Moll, H. (1995): ‘The immune functions of epidermal Langerhans cells’ (Springer Verlag, 1995), pp. 1–190Google Scholar
  10. Nakazawa, K., Nakazawa, H., Sahuc, F., Lepavec, A., Collombel, C., andDamour, C. (1997): ‘A novel pigmented human skin equivalent: new method of reconstitution by grafting an epithelial sheet onto a non-contractile dermal equivalent’,Pigment Cell Res. (in press)Google Scholar
  11. Olsson, M. J., Moellmann, G., Lerner, A. B., andJuhlin, L. (1994): ‘Vitiligo: Repigmentation with cultured melanocytes after cryostorage’,Acta Derm. Venerol. (Stockh),74, pp. 226–228Google Scholar
  12. Régnier, M., Pruniéras, M., andWoodley, D. (1981): ‘Growth and differentiation of adult human epidermal cells on dermal substrates’,Front Matrix Biol.,9, pp. 4–35Google Scholar
  13. Régnier, M., andSchmidt, R. (1994): ‘Reconstitution of an epidermal melanin unit by co-cultures of normal human keratinocytes (NHK) and normal human melanocytes (NHM)’,J. Invest. Dermatol. 102, p. 596Google Scholar
  14. Régnier, M., Schweizer, J., Michel, S., Bailly, C., andPrunieras, M. (1986): ‘Expression of high molecular weight (67 K) keratin in human keratinocytes cultured on dead de-epidermised dermis’,Exp. Cell Res.,165, pp. 63–72CrossRefGoogle Scholar
  15. Rheinwald, J. G., andGreen, H. (1975): ‘Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinocyte colonies from single cells’,Cell,6, pp. 331–344CrossRefGoogle Scholar
  16. Rowden, G., Lewis, M. G., andSullivan, A. K. (1977): ‘Ia antigen expression on human epidermal Langerhans cells’,Nature,268, pp. 247–248CrossRefGoogle Scholar
  17. Rowden, G., Colp, P., Dean, S., Auger, F., andLopes Valle, C. (1992): ‘Comparative epidermal Langerhans cell migration studies in epidermal and epidermal/dermal equivalent grafts’,J. Invest. Dermatol.,99, pp. 59S-61SCrossRefGoogle Scholar
  18. Schmidt, R. (1990): ‘Reconstructed human skin’in Schmidt, R. (Ed.): ‘Skin pharmacology’,Pharmacol.,3, 65–148Google Scholar
  19. Stingl, G., Katz, S. I., Green, I., andShevach, E. M. (1980): ‘The functional role of Langerhans cells’,J. Invest. Dermatol.,74, pp. 315–318CrossRefGoogle Scholar
  20. Strunk, D., Rappersberger, K., Egger, C., Strobl, H., Krömer, E., Elbe, A., Maurer, D., andStingl, G. (1996): ‘Generation of human dendritic cells/Langerhans cells from circulating CD34+ haematopoietic progenitor cells’,Blood,87, pp. 1292–1302Google Scholar
  21. Todd, C., Hewitt, S. D., Kempenaar, J., Noz, K., Thody, A. J., andPonec, M. (1993): ‘Co-culture of human melanocytes and keratinocytes in a skin equivalent model: effect of ultraviolet radiation’,Arch. Dermatol. Res.,285, pp. 455–459CrossRefGoogle Scholar
  22. Topol, B. M., Haimes, H. B., Dubertret, L., andBell, E. (1986): ‘Transfer of melanosomes in a skin equivalent modelin vitro’,J. Invest. Dermatol.,87, pp. 642–647CrossRefGoogle Scholar
  23. Valyi-Nagy, I. T., Murphy, G. F., Mancianti, M. L., Whitaker, D., andHerlyn, M. (1990): ‘Phenotypes and interactions of human melanocytes and keratinocytes in an epidermal reconstruction model’,Lab. Invest.,62, pp. 314–324Google Scholar

Copyright information

© IFMBE 1998

Authors and Affiliations

  • M. Régnier
    • 1
  • A. Patwardhan
    • 2
  • A. Scheynius
    • 2
  • R. Schmidt
    • 1
  1. 1.Life Science ResearchCentre Charles ZviakClichyFrance
  2. 2.Laboratory Medicine Division of Clinical ImmunologyKarolinska Institute and HospitalStockholmSweden

Personalised recommendations