Growth Hormone-Induced Stimulation of Multilineage Human Hematopoiesis

¹ Gladstone Institute of Virology and Immunology
² Gladstone Institute of Virology and Immunology and Department of Medicine, University of California, San Francisco
³ Gladstone Institute of Virology and Immunology; Departments of Medicine and Microbiology and Immunology, University of California at San Francisco Gladstone Institute of Virology and Immunology, University of California at San Francisco

^* To whom correspondence should be addressed. E-mail: mmccune{at}gladstone.ucsf.edu.

	Abstract

Growth hormone (GH) has been previously 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 (HIV-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 (IL)-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 anti-apoptotic 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.

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