HUMAN BONE-MARROW MICROVASCULAR ENDOTHELIAL-CELLS SUPPORT LONG-TERM PROLIFERATION AND DIFFERENTIATION OF MYELOID AND MEGAKARYOCYTIC PROGENITORS

Endothelial cells are a major component of the bone marrow (BM) microe nvironment that regulate the trafficking and homing of hematopoietic p rogenitor and stem cells. In this paper, we provide evidence that BM e ndothelial cells (BMECs) also support multilineage hematopoiesis by el aboration of soluble cytokines, Hematopoietic progenitor cells incubat ed in direct contact with BMEC monolayers, or physically separated by microporous membrane, expanded fivefold to sevenfold at 7 days, in the absence of exogenous cytokines. Flow cytometric analysis of prolifera ting progenitor cells grown in the presence of BMEC monolayers showed that by day 14 of coculture, 70% to 80% of hematopoietic cells were my eloid, expressing CD15 or CD14, and 14% to 19% were megakaryocytic, ex pressing GPIIb/IIIa or GPIb. CD34(+) cells derived from umbilical cord blood, cultured in the upper chamber of transwell culture plates, as well as the cells grown in direct contact with BMEC monolayers, genera ted progenitors for up to 70 days. Unstimulated BMEC monolayers consti tutively produce interleukin-6, Kit-ligand, granulocyte colony-stimula ting factor, and granulocyte macrophage colony-stimulating factor. The se data suggest that BMEC regulate proliferation of hematopoietic prog enitor cells and long-term culture initiating cells by elaboration of lineage-specific cytokines. (C) 1995 by The American Society of Hemato logy.