Report

Journal of Investigative Dermatology (1983) 81, 2s–10s; doi:10.1111/1523-1747.ep12539993

The Reconstitution of Living Skin

Eugene Bell1, Stephanie Sher1, Barbara Hull1, Charlotte Merrill1, Seymour Rosen2, Annette Chamson1,3, Daniel Asselineau1,4, Louis Dubertret5, Bernard Coulomb, Charles Lapiere7, Betty Nusgens and Yves Neveux6

  1. 1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, U.S.A.
  2. 2Pathology Department, Beth Israel Hospital, Harvard Medical School, and the Charles A. Dana Research Institute, Boston, Massachusetts, U.S.A.
  3. 3Laborotoire de Biochimie, UER de Médecine, St Etienne Cedex, France
  4. 4CIRD, Sophia Antirolis, Valbonne Cedex, France
  5. 5Service de Dermatologie, Hôpital Henri Mondor, Creteil, France
  6. 6Centre de Recherches de Service de Sante des Armees, Clamart, France
  7. 7Hôpttal de Bavine, Clinique Dermatologique, Université de Liege, Liege, Belgium
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Abstract

A living-skin equivalent useful as a skin replacement and as a model system for basic studies has been fabricated and tested extensively, it consists of two components: (1) a dermal equivalent made up of fibroblasts in a collagen matrix that is contracted and modified by the resident cells, and (2) an epidermis that develops from keratinocytes "plated" on the dermal equivalent. A multilayered keratinizing epidermis with desmosomes, tonofliaments, and hemidesmosomes forms. Basement lamella formation occurs within 2 weeks in vitro when rat cells are used, With human cells, crypt or pseudofollicular morphogenesis is observed in vitro within 3 weeks after plating cells on the dermal equivalent. Autografts and isografts of rat-skin equivalents made with cultured cells from biopsies are rapidly vascularized, block wound contraction, and persist essentially for the lifespan of the host. Seven to 9 days after grafting, donor cells become activated biosynthetically and mitotically. By 1 year, the dermal population decreases to a normal level and the matrix has been extensively remodeled, The grafts remain free of hair and sebaceous glands. Grafts to rats have been in place for over 2 years. Now, allografts of dermal equivalents have been made across a major histocompatibility barrier and are not rejected. The persistence of cellular elements of the grafts is monitored by use of a genetic marker, Challenge of the allograft with a second skin-equivalent graft after 1 month does not result in rejection of the original graft or of the second skin-equivalent graft. We propose that allografts of tissue equivalents are tolerated because cells with class II antigens are selected against during in vitro cultivation and are excluded from the graft. Thus the fabrication of skin-equivalent tissues or of other equivalent tissues with parenchymal cells that do not bear class II antigens may render transplants of such tissues immunologically acceptable despite the presence of allogeneic cells. The capacity to graft across major histocompatibility barriers using living tissue equivalents may have important clinical significance.

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References

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  2. Bell, E, Ehrlich, HP, Buttle, DJ, Nakatsuji, T: A living tissue formed in vitro and accepted as a full thickness skin equivalent. Science 1981 211: 1042–1054,
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  5. Coulomb, B, Dubertret, L, Bell, E, Merrill, C, Fosse, M, Breton-Gorius, J, Prost, C, Touraine, R: Endogenous peroxidases in normal human dermis: A marker of fibroblast function. J Invest Dermatol (in press)
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  21. Neveux, Y, Coulomb, B, Dubertret, L, Bell, E: Unpublished results

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