The reconstitution of living skin.

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, tonofilaments, 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.

[1]  Lafferty Kj Immunogenicity of foreign tissues. , 1980 .

[2]  B. Hull,et al.  Structural integration of skin equivalents grafted to Lewis and Sprague-Dawley rats. , 1983, The Journal of investigative dermatology.

[3]  P. Lipsky,et al.  Accessory cells unrelated to mononuclear phagocytes and not of bone marrow origin. , 1982, Immunology today.

[4]  E. Shevach,et al.  Analogous functions of macrophages and Langerhans cells in the initiation in the immune response. , 1978, The Journal of investigative dermatology.

[5]  B. Hull,et al.  Fibroblasts in isogeneic skin equivalents persist for long periods after grafting. , 1983, The Journal of investigative dermatology.

[6]  L. Braathen Studies on human epidermal Langerhans cells , 1980, The British journal of dermatology.

[7]  R. Timpl,et al.  Variability in collagen and fibronectin synthesis by scleroderma fibroblasts in primary culture. , 1981, The Journal of investigative dermatology.

[8]  E. Thorsby,et al.  Studies on Human Epidermal Langerhans Cells , 1980, Scandinavian journal of immunology.

[9]  B. Hull,et al.  Regulation of proliferation of fibroblasts of low and high population doubling levels grown in collagen lattices , 1981, Mechanisms of Ageing and Development.

[10]  E. Engleman,et al.  Cultured human epidermal cells do not synthesize HLA-DR. , 1982, The Journal of investigative dermatology.

[11]  E Bell,et al.  Living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness. , 1981, Science.

[12]  B. Hull,et al.  ACCEPTANCE OF ALLOGENEIC FIBROBLASTS IN SKIN EQUIVALENT TRANSPLANTS , 1983, Transplantation.

[13]  B. Hull,et al.  Development and Use of a Living Skin Equivalent , 1981, Plastic and reconstructive surgery.

[14]  E Bell,et al.  Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Steinmuller Passenger leukocytes and the immunogenicity of skin allografts. , 1980, The Journal of investigative dermatology.