Abnormal proliferation and aging of cultured fibroblasts from pigs with subcutaneous fibrosis induced by gamma irradiation.

In vivo, fibrotic disorders, which may be due either to injury or disease, are characterized by overproliferation of fibroblasts and overproduction of connective tissue. In vitro, however, most of the fibrotic cell lines studied exhibited no differences in growth potential compared with control cell lines derived from normal skin. In the present study, we investigated the in vitro behavior of fibroblasts derived from pigs with subcutaneous fibrosis induced by gamma irradiation. The cells were isolated from the scar tissue six to 20 months after irradiation. In primary cultures, the cells derived from the fibrotic lesions exhibited greater attachment efficiency and faster proliferation than those of the cells derived from the normal skin of the same animal. In long-term cultures, the differences between normal and fibrotic cells were still greater: the normal skin cells underwent 17 population doublings and then died, whereas the fibrotic cells exhibited a prolonged lifespan, and were still actively proliferating after 80 population doublings. Cell morphology and the number of chromosomes were modified throughout subcultures. These results imply that in the scar tissue active fibrotic cell proliferation continued for years after irradiation and that this activation was expressed in vitro. Therefore, in this pig fibrosis model, the data acquired in the present in vitro studies closely resemble that obtained from earlier in vivo observations.