Flt3 ligand stimulates/costimulates the growth of myeloid stem/progenitor cells

H. E. Broxmeyer, L. Lu, S. Cooper, L. Ruggieri, Z. H. Li, S. D. Lyman

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133 Scopus citations

Abstract

The present studies evaluated effects of recombinant human (rhu) and murine (rmu) flt3 ligand (flt3-L) on colony formation by subsets of myeloid stem and progenitor cells present in low-density (LD) and cell-sorted CD34+++ hu cord blood (CB) and bone marrow (BM) cells and unseparated mu BM cells. By itself, flt3-L had weak colony-stimulating activity. It stimulated small dispersed CFU-GM-type colonies, but not BFU-E, CPU-GEMM, or HPP-CFC colonies, from LD and CD34+++ huCB and BM. However, flt3-L had additive to greater-than-additive effects on colony number and size by CFU-GM stimulated with GM-CSF or IL-3, with or without Steel factor (SLF); by CFU-G stimulated by G-CSF with or without: SLF; by CFU-M stimulated by CSF-1; and by BPU-E, CFU-GEMM, and HPP-CFC stimulated by Epo with or without IL-3 or SLF. Flt3-L enhanced the effects of SLF, alone and in combination with other CSFs. Similar effects were apparent on LD and sorted CD34+++ cells and also at the level of single sorted and isolated CD34+++ cells/well. Flt3-L enhanced expansion of immature subsets of huCD34+-column separated CB CFU-GM stimulated by the potent combination of SLF and PIXY321 (a GM-CSF/IL-3 fusion protein). While flt3-L did not enhance the replating capacity of CFU-GEMM plated in the presence of Epo and SLF, it enhanced numbers of these CFU-GEMM colonies with the capacity to be replated. Flt3-L effects were not species-specific; rhu and rmu forms were active on huCB/BM and muBM. These results demonstrate the potent direct-acting stimulating/costimulating activities of flt3-L in vitro on myeloid stem/progenitor cells.

Original languageEnglish (US)
Pages (from-to)1121-1129
Number of pages9
JournalExperimental Hematology
Volume23
Issue number10
StatePublished - Jan 1 1995

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Keywords

  • Flk-2 ligand
  • Plt3 lisand
  • Stem/progenitor cells

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Broxmeyer, H. E., Lu, L., Cooper, S., Ruggieri, L., Li, Z. H., & Lyman, S. D. (1995). Flt3 ligand stimulates/costimulates the growth of myeloid stem/progenitor cells. Experimental Hematology, 23(10), 1121-1129.