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Bone marrow stromal cells produce thrombopoietin and stimulate
megakaryocyte growth and maturation but suppress proplatelet formation
H Nagahisa, Y Nagata, T Ohnuki, M Osada, T Nagasawa, T Abe and K Todokoro
Tsukuba Life Science Center, Institute of Physical and Chemical Research
(RIKEN), Ibaraki, Japan.
Production of blood cells is regulated by the interplay of various
cytokines and bone marrow stromal cells. Recently, a ligand for the orphan
receptor Mpl was identified as thrombopoietin (TPO), which specifically
regulates megakaryocyte differentiation, and it was reported to be
expressed mainly in liver and kidney. As it was found that thrombopoietin
is also produced in bone marrow stromal cells, we studied further the roles
of bone marrow stromal cells on megakaryocytopoiesis and platelet
formation. The stromal cells stimulated growth and maturation of
bone-marrow-derived megakaryocytes in the presence of thrombopoietin, and
also supported growth of BaF3 cells expressing exogenous Mpl without
thrombopoietin. Thrombopoietin induces drastic morphological change of
megakaryocytes in bone marrow cells in vitro, ie, the formation of lengthy
beaded cytoplasmic processes (proplatelet formation). However, when the
purified megakaryocytes were cocultured with the stromal cells with or
without thrombopoietin, most of the megakaryocytes adhered to the stromal
cells and remained unchanged, while free megakaryocytes induced proplatelet
formation. These observations indicated that the stromal cells in a
hematopoietic microenvironment in bone marrow secrete thrombopoietin and
stimulate proliferation and maturation of megakaryocytes, but the
interaction of megakaryocytes with the stromal cells may suppress
proplatelet formation.
Volume 87,
Issue 4,
pp. 1309-1316,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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