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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3703-3712
Thrombopoietin Augments Stem Cell Factor-Dependent Growth of Human
Mast Cells From Bone Marrow Multipotential Hematopoietic Progenitors
Nobukuni Sawai,
Kenichi Koike,
Hadija Hemed Mwamtemi,
Tatsuya Kinoshita,
Yumi Kurokawa,
Kazuo Sakashita,
Tsukasa Higuchi,
Kouichi Takeuchi,
Masaaki Shiohara,
Takehiko Kamijo,
Susumu Ito,
Takashi Kato,
Hiroshi Miyazaki,
Tetsuji Yamashita, and
Atsushi Komiyama
From Department of Pediatrics, Shinshu University School
of Medicine, Matsumoto, Japan; Blood Transfusion Service, Shinshu
University Hospital, Matsumoto, Japan; Pharmaceutical Research
Laboratory, Kirin Brewery Co, Ltd, Takasaki, Japan; and Research & Development, Mitsubishi Kagaku Bio-Clinical Laboratories, Inc, Tokyo,
Japan.
The effects of thrombopoietin (TPO) and/or stem cell factor (SCF) on
the development of human mast cells from CD34+ bone
marrow (BM) cells were investigated using a serum-deprived liquid
culture system. Mast cells were identified by measurement of
intracellular histamine content, immunocytochemical staining, and flow
cytometric analysis. Whereas SCF alone generated only a small number of
tryptase+ cells, the addition of TPO to the culture
containing SCF resulted in an apparent production of mast cells from 3 weeks until at least 15 weeks. Some of the cells reacted with an
antichymase monoclonal antibody as well. Based on the effects of growth
factor(s) on a later phase of the mast cell growth, TPO may stimulate
an early stage of mast cell development in combination with SCF, whereas subsequent growth seems to be supported by SCF alone. Single-cell culture studies indicated that the
CD34+CD38 c-kit+ cells and
CD34+CD38+c-kit+ cells were
responsible for the SCF + TPO-dependent mast cell production.
Two-step culture assays clearly showed that mast cells originated from
multilineage colony-forming cells that had potential to differentiate
into neutrophil/mast cell lineages, neutrophil/macrophage/mast cell
lineages, or neutrophil/macrophage/mast cell/erythroid lineages. These
results suggest that TPO plays an important role in the development of
human mast cells from CD34+ BM cells in concert with SCF,
and provide direct evidence of the differentiation into the mast cell
lineage of human multipotential BM-derived progenitors.
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