title: Thrombopoietin augments stem cell factor-dependent growth of human mast cells from bone marrow multipotential hematopoietic progenitors.
abstract: 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.
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sawai
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: H H
authors.initials: HH
authors.lastname: Mwamtemi
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Y
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: K
authors.initials: K
authors.lastname: Sakashita
authors.forename: T
authors.initials: T
authors.lastname: Higuchi
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: M
authors.initials: M
authors.lastname: Shiohara
authors.forename: T
authors.initials: T
authors.lastname: Kamijo
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: A
authors.initials: A
authors.lastname: Komiyama
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008407:Mast Cells / Q000166:cytology*; D019089:Stem Cell Factor / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology*
chemical_list: D019089:Stem Cell Factor; D013926:Thrombopoietin