Autocrine growth regulation in fetal and adult human fibroblasts

Medium conditioned (CM) by human fetal fibroblasts stimulates proliferation in sparse cultures. This effect is inhibited by suramin and staurosporine, indicating the presence of autocrine growth factors in CM. On the contrary, CM inhibits DNA synthesis in confluent cultures, suggesting a regulatory role for the secreted factors. The growth regulatory profile of CM persists during in vitro ageing. However, it changes dramatically during the fetal-to-adult transition, as adult human fibroblasts are stimulated by CM, regardless of the culture density. These effects are similar to those that TGF-beta is known to have on fetal and adult human fibroblasts. Indeed TGF-beta is present in media conditioned by human fibroblasts, but CM-activity cannot be ascribed solely to this factor. Fibroblasts originating from different tissues exhibit the same autocrine regulatory features, suggesting the general character of this mechanism.