TRANSPLANTATION OF SKIN 111 parting to their progeny the necessary instructions how to differentiate and (b) germinal cells in the basal layer of all types of epidermal epithelia in the body are equipotential, their differentiative behavior being de- termined by interaction with the particular type of dermis that forIns their substrate, i.e., the source of the specificity expressed by the epider- mis at a particular site is determined by the dermis. The purpose of this contribution is to review various types of grafting experiments which have been conducted to discriminate between these possibilities, and to analyze the basis of a genetic defect which is expressed in an epidermal component in mammals. STUDIES ON "FITTED" SPLIT-THICKNESS CJRAFTS OF DIFFERENT TYPES OF SKIN TRANSPLANTED HETEROTOPICALLY In various laboratory rodents, notably in guinea pigs, hamsters, mice, and rabbits, experiments have been carried out in which relatively thin grafts of skin having regionally distinctive properties have been trans- planted as good "fits" to anatomically unnatural recipient areas prepared in the skin of the trunk or elsewhere on genetically compatible hosts (5, 6). Provided that certain purely technical requirements are met, such grafts heal-in well and maintain their original specificity of epidermal type in- definitely. For example, the skin of the sole of a guinea pig's foot is much like that of man. When transplanted to a site on the side of a guinea pig's chest, where it is protected by hairs, its epidermis maintains its high rate of proliferation and continues to produce a thick, tough and now functionally useless cuticle. Likewise, if a sheet of the highly vascular semitransparent "skin" that constitutes the wall of a Syrian hamster's cheek pouch is transplanted to its trunk, the graft faithfully conserves its original properties in its new environment. These findings certainly tell us that all the information required to determine the pattern of stratig- raphy, etc., of the epidermis is included within the transposed pieces of skin. A shortcoining of this type of experiment is that the so-called "split-thickness" grafts employed necessarily include some connective tis- sue or dermis. Unfortunately, although it is possible to separate shavings of skin into their epidermal and dermal moieties with the aid of enzymes, notably trypsin, grafts of pure epidermis, transplanted to wound beds prepared by excision of the entire thickness of the skin, fail to prevent contracture of the grafted site (7, 8). Therefore, they are lost nonspecifi- cally before they can tell us much about their capacity to maintain their specific microanatomical structure as their component cells proliferate and differentiate.

112 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS STUDIES ON SPLIT-THICKNESS SKIN GRAFTS TRANSPLANTED HETEROTOPICALLY IN OPEN STYLE TO EXTENSIVE, FULL-THICKNESS BEDS ON RABBITS' CHESTS Because of their size it is possible to prepare relatively large, full- thickness wounds on the sides of rabbits' chests, up to about 5 X 8 cm, in which there is no residual trunk skin dermis (6). Maintained under appropriate dressings, highly vascular granulation tissue develops over these wounds which take about 20 to 25 days to contract to narrow re- sidual scars (7). If small, thin, split-thickness grafts of various types of skin are trans planted to the centers of such large wounds, epithelium, unaccompanie{l by connective tissue, grows out from their margins over the favorabh' milieu afforded by the granulation tissue which forms an ad hoc mesen- chymal substrate. This enables one to compare, both macroscopically and microscopically, the types of epidermis that migrate out from qualita- tively different kinds of skin over the common, anatomically unnatural substitute for dermis afforded by granulation tissue. This approach has yielded highly suggestive evidence that the germinal layers of tongue, cornea, ear skin, and vaginal epidermis must differ intrinsically with re- spect to the properties of the epidermis they can generate (9, 10). For example, on such wounds newly formed corneEl epidermis maintains its transparency, that of tongue produces a thick, tough compact cuticle at the surface and the overall "staining" and other properties of its more proximal cells are like those o.f normal tongue epidermis. Epithelial out- growth from ear skin produces a waxy-looking, flaking cuticle. There are other differences, of course, at the microscopic level which we i•eedn't go into. Unfortunately, as already mentioned, wound contracture, which cannot easily be overcome, restricts the duration of this type of experi- ment to about three weeks. This period is not long enough to. rule out the possibility that the observed conservation of original specificity on the part of the various types of outgrowing epidermal epithelia is due to the continued presence of inductive stimuli of dermal origin which have not yet "diluted out" completely as the cells with which they are asso- ciated divide, migrate, and differentiate. STUDIES ON DERMo-EPIDERMAL RECOMBINANT GRAFTS What has proved to be the most informative and definitive means of analyzing the basis of epidermal specificities in adult skin entails the production of "heterotypic recombinant" skin ,grafts in guinea pigs and