FROM NEWBORN TO ADULT - PHENOTYPIC AND FUNCTIONAL-PROPERTIES OF SKIN EQUIVALENT AND HUMAN SKIN AS A FUNCTION OF DONOR AGE

The skin's most important function is to act as a barrier against flui d loss, microorganism infections, and percutaneous absorption. To fulf ill this role, keratinocytes proliferate and differentiate reproduce a protective layer: the stratum corneum. Because stem cells are respons ible for the production of differentiated progeny and stem cells (K19- expressing cells) are less abundant in skin from older donors, the pur pose of this study was to establish whether histological and functiona l properties of differentiating skin is influenced by donor age. The i n vitro model developed for the evaluation of skin properties (Michel et al., 1995) was used to produce skin equivalents from newborn, child , and adult keratinocytes. Throughout maturation, skin equivalents wer e compared with corresponding skin biopsies for keratin, filaggrin, an d transglutaminase expression. Percutaneous absorptions of hydrocortis one also were measured and correlated with lipid content. After 1 wk o f immersed culture, the epidermal layer of newborn skin equivalents wa s thicker than child and adult epidermis. As expected, a greater propo rtion of cutaneous stem cells was present in newborn compared with chi ldren and adult skin equivalents. No age-related difference was observ ed for differentiation markers. When skin equivalents were cultured at the air-liquid interface, cell differentiation and stratum corneum fo rmation were induced, and the age-related variation in the thickness o f the epidermal layer disappeared. Percutaneous absorption through the se matured skin equivalents did not vary with age. Their lipid density and profile were similar. Accordingly; skin biopsies exhibited compar able percutaneous absorption profiles independently of donor age. In c onclusion, although newborn skin equivalents, or skin biopsies, contai ned more stem cells than child and adult counterparts, no age-related histological difference was observed in the differentiated tissues. Mo reover, the functional barrier property of skins and matured skin equi valents did not vary with age. Therefore, both newborn and adult kerat inocytes produce useful in vitro models to study epidermal differentia tion processes involved in both normal and pathological states. (C) 19 97 Wiley-Liss, Inc.