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Human bone marrow microvascular endothelial cells support long-term
proliferation and differentiation of myeloid and megakaryocytic progenitors
S Rafii, F Shapiro, R Pettengell, B Ferris, RL Nachman, MA Moore and AS Asch
Department of Hematology-Oncology, New York Hospital-Cornell Medical Center
10021, USA.
Endothelial cells are a major component of the bone marrow (BM)
microenvironment that regulate the trafficking and homing of hematopoietic
progenitor and stem cells. In this paper, we provide evidence that BM
endothelial cells (BMECs) also support multilineage hematopoiesis by
elaboration of soluble cytokines. Hematopoietic progenitor cells incubated
in direct contact with BMEC monolayers, or physically separated by
microporous membrane, expanded five-fold to sevenfold at 7 days, in the
absence of exogenous cytokines. Flow cytometric analysis of proliferating
progenitor cells grown in the presence of BMEC monolayers showed that by
day 14 of coculture, 70% to 80% of hematopoietic cells were myeloid,
expressing CD15 or CD14, and 14% to 19% were megakaryocytic, expressing
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, generated progenitors for up
to 70 days. Unstimulated BMEC monolayers constitutively produce
interleukin-6, Kit- ligand, granulocyte colony-stimulating factor, and
granulocyte macrophage colony-stimulating factor. These data suggest that
BMEC regulate proliferation of hematopoietic progenitor cells and long-term
culture initiating cells by elaboration of lineage-specific cytokines.
Volume 86,
Issue 9,
pp. 3353-3363,
11/01/1995
Copyright © 1995 by The American Society of Hematology
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