Fibroblast selection in scleroderma. An alternative model of fibrosis

Abstract

Human preputial skin fibroblasts were cloned in vitro, and studies in 21 clones were shown to exhibit a 3-fold difference in collagen synthesis; this heterogeneity of phenotypic expression was conserved over multiple population doublings. When the clones were exposed to sera from 10 scleroderma patients, selective growth of high-collagen-producing fibroblasts was observed. Prostaglandin E2 abrogated the selective effect of scleroderma serum on high-collagen-producing fibroblast clones. Besides enhanced collagen synthesis, these clones of normal fibroblasts shared an insensitivity to feeding schedule with fibroblasts from scleroderma skin. These data raise the possibility that scleroderma represents a process of selection of fibroblasts programmed to produce increased amounts of collagen.