Effects of keratinocyte growth factor on in vitro engineered, genetically modified human epidermis: paracrine versus autocrine actions

Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial morphogenesis and reepithelialization following burn or injury. We used recombinant retroviruses to introduce the KGF gene in an in vitro engineered human epidermis and evaluated its potential as a wound-healing factor. In addition, we examined the effects of exogenously added KGF (paracrine) and KGF secreted by modified keratinocytes (autocrine). Microscopic evaluation of tissue sections showed KGF-expressing (modified) and KGF-treated (exogenous KGF) grafts with pronounced hyperthickening, elongation of the basal cells and flattening of the rete-ridges, as compared to controls. KGF induced a ripple-like pattern in the junction of stratum corneum and granular layers, similar to the rete-ridge pattern of unmodified grafts. Quantitative immunostaining revealed that KGF significantly increased proliferation of basal and suprabasal cells, similar to a psoriatic epidermis. In addition, KGF delayed the differentiation program of stratified epidermis, as suggested by the expression patterns of differentiation specific markers. All grafts developed an effective barrier as evaluated by measurements of surface hydration