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Hepatocyte growth factor as a hematopoietic regulator
T Nishino, H Hisha, N Nishino, M Adachi and S Ikehara
Cellular Technology Institute, Otsuka Pharmaceutical Co, Ltd, Tokushima,
Japan.
Hepatocyte growth factor (HGF) was originally isolated as a mitogen for
adult hepatocytes, but this cytokine is now regarded as a multi- functional
factor. In the present study, we show that the mouse liver in the middle
and/or late stage of the fetal life expresses both HGF and c-met (its
receptor) messages. HGF and c-met mRNA are coexpressed not only in the
adherent layers of fetal liver long-term cultures (FL- LTCs) and adult bone
marrow long-term cultures (BM-LTCs), but also in the stromal cell lines
MS-5 and PA-6. Addition of human HGF (2 and 20 ng/mL) to the LTCs enhances
(1) nonadherent cell counts (ninefold in FL- LTCs and sixfold in BM-LTCs),
(2) nonadherent colony-forming unit-in culture (CFU-C) counts (eightfold in
FL-LTCs and fivefold in BM-LTC), and (3) cobblestone colony counts.
However, HGF slightly inhibits the proliferation of stromal cells. No
direct effect of HGF on freshly isolated BM and/or FL cells is found in the
CFU-C assay. However, an approximately 1.5-fold synergistic increase in
CFU-C counts is noted when the BM or FL cells are cocultured with HGF in
the presence of interleukin-3. These findings strongly suggest that HGF
plays a crucial role as a hematopoietic regulator in the proliferation and
differentiation of hematopoietic progenitors.
Volume 85,
Issue 11,
pp. 3093-3100,
06/01/1995
Copyright © 1995 by The American Society of Hematology
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