Insulin-like Growth Factors Promote DNA Synthesis and Support Cell Viability in Fetal Hemopoietic Tissue by Paracrine Mechanisms

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Abstract
There is significant evidence that the insulin-like growth factors (IGF) play a role in both murine and human hemopoiesis. In order to better define the nature and mechanisms of these effects, we have used a serum-free system to examine DNA synthesis and cell replication in murine hemopoietic cells. Cell preparations from 13-day fetal mice livers were incubated in serum-free DMEM alone or with erythropoietin (Epo) 0.5 U/ml, recombinant human IGF-I, purified IGF-II, or recombinant human growth hormone (GH) in various doses, and [3H]thymidine added for the last 3 hr of 21-hr incubation. Cell distribution was over 80% erythroid or erythroblasts. IGF-I and IGF-II promoted thymidine incorporation into cells at a half-maximal dose of 3 and 1 nM respectively, IGF-II with a maximum potency 65% of IGF-I; insulin stimulated at a half-maximum dose of 100 nM, with similar maximum effect to IGF-I, and their effects were not additive. GH was stimulatory at 1 microM. Epo was 2-9 times as effective as IGF-I and their effects were not additive. A monoclonal antibody to IGF-I reduced the effect of IGF-I by 50-80%, had no effect on Epo, and abolished the GH effect. Separation of erythroid cells and precursors from accessory and other liver cells did not alter the response to IGF-I. Cell counts increased in response to IGF-I or Epo, and cell viability was maintained by IGF-I compared to control medium.(ABSTRACT TRUNCATED AT 250 WORDS)

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