REGENERATIVE HEALING OF INCISIONAL WOUNDS IN MURINE FETAL LUNGS MAINTAINED IN ORGAN-CULTURE

Although fetal dermal repair is known to be fundamentally different fr om adult healing, the response to wounding in other organs is less wel l characterized. Scarless repair in mid-gestation dermis with a transi tion to adult-type healing at term has been shown in fetal organ cultu re. A lung explant culture system was used to investigate whether woun d repair in the fetal lung shows characteristics similar to those foun d in fetal dermis. Lungs from 14-day and 18-day CD-1 murine fetuses an d 21-day-old newborns, (term = 20 days, n = 24) were wounded by linear incision and incubated at 37 degrees C, in a 21% O-2, 5% CO2 environm ent, in BGJb supplemented with vitamin C and antibiotics. Medium was c hanged daily. Samples were fixed at 7 days and embedded in paraffin. S ections were stained with hematoxalyn-eosin and Masson Trichrome. Addi tional 14-day and 18-day samples were frozen in freon and immunohistoc hemical staining for TGF-beta performed. Other frozen tissues from eac h time point were homogenized and used to assay for endogenous TGF-bet a levels by Western blot analysis. Histology showed reconstitution of tissue architecture across the wound in 14 day and 18-day specimens. I n representative histological sections, intact bronchial architecture developed across the previous wound site. No cellular inflammatory res ponse was observed, and collagen deposition was undetectable at the si te of the wound by Trichrome staining. By 22 days the lung explants sh owed a much less ordered repair, including disorganized collagen depos ition. Immunohistochemistry showed TGF-beta throughout the lung parenc hyma of 14 day and 18 day lungs without recruitment at the wound site. Western blotting showed a marked increase in signal for TGF-beta in 1 8-day compared to 14-day explants. A smaller increase was seen from 18 days to 22 days. The authors conclude that the murine fetal lung show s scarless repair even late into gestation. This implies a plasticity in lung not seen in the integument, as well as an ability of tissues t o exert a strong degree of local control over the healing response. Co pyright (C) 1995 by W.B. Saunders Company.