Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner

The aim of this study was to explore further the hypothesis that early stag es of normal human hematopoiesis might be coregulated by autocrine/paracrin e regulatory loops and by cross-talk among early hematopoietic cells. Highl y purified normal human CD34(+) cells and ex vivo expanded early colony-for ming unit-granulocyte-macrophage (CFU-GM)-derived, burst forming unit-eryth roid (BFU-E)-derived, and CFU-megakaryocyte (CFU-Meg)-derived cells were ph enotyped for messenger RNA expression and protein secretion of various grow th factors, cytokines, and chemokines to determine the biological significa nce of this secretion. Transcripts were found for numerous growth factors ( kit ligand [KIL], FLT3 ligand, fibroblast growth factor-2 [FGF-2], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], insulinl ike growth factor-1 [IGF-1], and thrombopoietin [TPO]); cytokines (tumor ne crosis factor-alpha, Fas ligand, interferon alpha, interleukin 1 [IL-1], an d IL-16); and chemokines (macrophage inflammatory protein-1 alpha [MIP-1 al pha], MIP-1 beta, regulated upon activation, normal T cell expressed and se creted [RANTES], monocyte chemotactic protein-3 [MCP-3], MCP-4, IL-8, inter feron-inducible protein-10, macrophage-derived chemokine [MDC], and platele t factor-4 [PF-4]) to be expressed by CD34(+) cells. More importantly, the regulatory proteins VEGF, HGF, FGF-2, KL, FLT3 ligand, TPO, IL-16, IGF-1, t ransforming growth factor-beta1 (TGF-beta1), TGF-beta2, RANTES, MIP-1 alpha , MIP-1 beta, IL-8, and PF-4 were identified in media conditioned by these cells. Moreover, media conditioned by CD34(+) cells were found to inhibit a poptosis and slightly stimulate the proliferation of other freshly isolated CD34(+) cells; chemo-attract CFU-GM- and CFU-Meg-derived cells as well as other CD34(+) cells; and, finally, stimulate the proliferation of human end othelial cells. It was also demonstrated that these various hematopoietic g rowth factors, cytokines, and chemokines are expressed and secreted by CFU- GM-, CFU-Meg-, and BFU-E-derived cells. It is concluded that normal human C D34(+) cells and hematopoietic precursors secrete numerous regulatory molec ules that form the basis of intercellular cross-talk networks and regulate in an autocrine and/or a paracrine manner the various stages of normal huma n hematopoiesis. (Blood. 2001;97:3075-3085) (C) 2001 by The American Societ y of Hematology.