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Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Burns Hospital, Boston, Massachusetts 02114, USA
2Correspondence: Shriners Hospitals for Children, 51 Blossom St., Boston, MA 02114, USA.
Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial
cell growth. To examine the direct effects of KGF on the morphogenesis
of the epidermis, we generated skin equivalents in vitro
by seeding human keratinocytes on the papillary surface of acellular
dermis and raising them up to the air-liquid interface. KGF was either
added exogenously or expressed by keratinocytes via a recombinant
retrovirus encoding KGF. KGF induced dramatic changes to the
3-dimensional organization of the epidermis including pronounced
hyperthickening, crowding, and elongation of the basal cells,
flattening of the rete ridges, and a ripple-like pattern in the
junction of stratum corneum and granular layers. Quantitative
immunostaining for the proliferation antigen, Ki67, revealed that in
addition to increasing basal proliferation, KGF extended the
proliferative compartment by inducing suprabasal cell proliferation.
KGF also induced expression of the integrin 
5ß1 and delayed
expression of keratin 10 and transglutaminase. However, barrier
formation of the epidermis was not disrupted. These results demonstrate
for the first time that a single growth factor can alter the
3-dimensional organization and proliferative function of an in
vitro epidermis. In addition to new strategies for tissue
engineering, such a well-defined system will be useful for analyzing
growth factor effects on the complex links between cell proliferation,
cell movement and differentiation within a stratified
tissue.—Andreadis, S. T., Hamoen, K. E., Yarmush, M. L., Morgan, J. R. Keratinocyte growth factor induces
hyperproliferation and delays differentiation in a skin equivalent
model system.
Key Words: KGF • fibroblast growth factor • cell proliferation • rete ridges
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