Göttingen minipigs were treated topically for 6 d with a novel
retinoid (
MDI 301) at concentrations ranging from 0.3% to 30% in cream vehicle. Treatment of the minipigs did not adversely affect their health (hematological and necropsy parameters) or produce changes in the skin suggestive of
retinoid-induced skin irritation. After killing the animals, skin samples from each treatment site were excised and maintained in organ culture for 6 d. In addition, untreated skin was also maintained in organ culture and treated with
MDI 301 (0.1-5 microg/ml). After 3 d, the culture supernatants were collected and analyzed for levels of
collagen type I and for
matrix metalloproteinases (
MMPs). Both skin samples treated in vivo and skin samples exposed to
MDI 301 in culture demonstrated increased
collagen production. Only slight changes in levels of MMP-2 (
gelatinase A) or MMP-9 (
gelatinase B) were seen. After 6 d, the organ-cultured skin was fixed in
formalin and prepared for histology. The organ-cultured skin was compared to skin that was fixed at killing after in vivo treatment. Epidermal
hyperplasia was quantified at various
MDI 301 concentrations. In vivo and in vitro treatments showed similar results-although the thickness was not substantially changed on average, there were focal areas of
hyperplasia at higher
retinoid concentrations. Taken together, these data suggest that
MDI 301 enhances
collagen production in minipig skin, without irritation. Furthermore, these studies suggest that minipig skin exposed to the
retinoid in organ culture is equally predictive as topically treated skin. The in vitro organ culture approach may provide a cost-effective alternative model to that of the intact animal for skin
retinoid testing.