Role of c-kit ligand in the expansion of human hematopoietic progenitor cells

J. Brandt, R. A. Briddell, E. F. Srour, T. B. Leemhuis, R. Hoffman

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

To test the hypothesis that the c-kit ligand plays an important role in the regulation of early events occurring during human hematopoiesis, we determined the effect of a recombinant form of c-kit ligand, termed mast cell growth factor (MGF), on the high-proliferative potential colony-forming cell (HPP-CFC) and the cell responsible for initiating long-term hematopoiesis in vitro (LTBMIC). MGF alone did not promote HPP-CFC colony formation by CD34+ DR- CD15- marrow cells, but synergistically augmented the ability of a combination of granulocyte-monocyte colony-stimulating factor (GM- CSF) interleukin (IL)-3 and a recombinant GM-CSF/IL-3 fusion protein (FP) to promote the formation of HPP-CFC- derived colonies. MGF had a similarly profound effect on in vitro long-term hematopoiesis. Repeated additions of IL-3, GM-CSF, or FP alone to CD34+ DR- CD15- marrow cells in a stromal cell-free culture system increased cell numbers 103- fold by day 56 of long-term bone marrow culture (LTBMC), while combinations of MGF with IL-3 or FP yielded 104- and 105-fold expansion of cell numbers. Expansion of the number of assayable colony-forming unit-granulocyte-monocyte (CFU-GM) generated during LTBMC was also markedly enhanced when MGF was added in combination with IL-3 or FP. In addition, MGF, IL-3, and FP individually led to a twofold to threefold increase in HPP-CFC numbers after 14 to 21 days of LTBMC. Furthermore, the effects of these cytokines on HPP-CFC expansion during LTBMC were additive. Throughout the LTBMC, cells receiving MGF possessed a higher cloning efficiency than those receiving IL-3, GM-CSF, or FP alone. These data indicate that the c-kit ligand synergistically interacts with a number of cytokines to directly augment the proliferative capacity of primitive human hematopoietic progenitor cells.

Original languageEnglish (US)
Pages (from-to)634-641
Number of pages8
JournalBlood
Volume79
Issue number3
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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