PRODUCTION OF INSULIN-LIKE-GROWTH-FACTOR-I (IGF-I) AND IGF-BINDING PROTEINS BY RAT INTESTINAL STROMAL CELLS IN-VITRO

To determine if intestinal stromal cells secrete diffusible factors su ch as insulin-like growth factors (IGFs) capable of regulating epithel ial cell growth in vitro, stromal cells were isolated by enzymatic dig estion of rat intestine. Incorporation of [H-3]thymidine into DNA and [C-14]leucine into protein of IEC-6 cells, a model intestinal epitheli al cell line, was significantly increased (two-to threefold) when the IEC-6 cells were co-cultured with stromal cells, relative to IEC-6 cel ls grown alone. Medium conditioned by stromal cells stimulated DNA syn thesis of IEC-6 cells in a dose-dependent manner. Analysis of the cond itioned medium revealed that intestinal stromal cells secreted IGF-I, but little IGF-II, in addition to an M-r, 32,000 IGF-binding protein ( IGFBP-2) and an IGFBP having M-r similar to 24,000. We conclude that r at intestinal stromal cells secrete one or more diffusible factors, wh ich may include IGF-I and IGFBPs, capable of stimulating proliferation of IEC-6 cells in vitro.