Growth Hormone–Induced Stimulation of Multilineage Human Hematopoiesis

Growth hormone (GH) has been shown to have significant positive effects on hemato‐lymphopoiesis in rodent models and, more recently, to increase thymic mass and circulating naïve CD4+ T cells in humans infected with the human immunodeficiency virus, type 1. To determine whether the latter effects on human T lymphopoiesis might be due, at least in part, to effects on the bone marrow (BM), we examined the specific effects of GH and its proximal mediator, insulin‐like growth factor I (IGF‐I), on human multilineage hematopoiesis in fetal BM (FBM). Using in vitro analysis, we found that GH and IGF‐I each stimulated the expansion of primitive multilineage CD34+CD38− hematopoietic progenitor cells and increased yields of several hematopoietic subpopulations, including CD34+CD38+CD10+ lymphoid progenitor cells. Additionally, GH and IGF‐I had direct effects on FBM stromal elements, inducing the expansion of myeloid‐like CD45+CD14+ FBM stromal cells and enhancing production of the hematopoietic cytokine interleukin‐3 by fibroblast‐like CD45−CD10+ FBM stromal cells. Surface expression of GH and type‐I IGF receptors correlated with the observed biologic responses to these hormones. Whereas GH enhanced the proliferation of FBM progenitors and stroma, IGF‐I exerted a predominantly antiapoptotic effect. Finally, both GH and IGF‐I stimulated the generation of hematopoietic colony forming cells. These findings identify specific targets of GH and IGF‐I within human FBM, and demonstrate direct and indirect effects that may contribute to GH‐mediated enhancement of human hemato‐lymphopoiesis.