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Growth Hormone–Induced Stimulation of Multilineage Human Hematopoiesis

^a Gladstone Institute of Virology and Immunology, San Francisco, California, USA;
^b Department of Medicine, University of California, San Francisco, California, USA;
^c Department of Microbiology and Immunobiology, University of California, San Francisco, California, USA

Key Words. Hematopoiesis • Growth factor • Hematopoietic progenitor • In vitro • Marrow stromal cells • Bone marrow cells

Correspondence: Joseph M. McCune, M.D., Ph.D., Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158-2261, USA. Telephone: 415-734-5060; Fax: 415-826-8449; e-mail: mmccune{at}gladstone.ucsf.edu

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.

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