Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells

Abstract

Recombinant rat stem cell factor (SCF) was studied for its ability to stimulate the growth of murine hematopoietic progenitor cells and to generate colony-forming cells (CFC) from highly enriched populations of hematopoietic cells. In serum-deprived cultures, SCF alone stimulated few colonies but interacted with a number of other hematopoietic growth factors, particularly interleukin 3, to promote colony formation. The most marked effect was on the generation of mixed-cell colonies. Hematopoietic cells were sorted into wheat-germ agglutinin-negative, monocyte-depleted, rhodamine 123 (Rh123)-bright or Rh123-dull cells. Historically, Rh123-bright cells are capable of short-term (<1 mo) marrow engraftment, whereas among Rh123-dull cells are cells capable of long-term marrow engraftment. Enriched cells (2.5 × 103) were placed into serum-deprived liquid cultures with various hematopoietic growth factors. Initially, the Rh123-bright and Rhl23-dull cells had few CFC but, in the presence of interleukin 3 and SCF, Rh123-bright cells gave rise to >15,000 granulocyte/macrophage CFC, >1500 erythroid burst- forming cells, and >700 mixed-cell CFC by day 5. In contrast, Rh123-dull cells proliferated only in the presence of interleukin 3 and SCF, but total cell numbers rose to a peak of 18,000 by day 21, and one-third of the cells were CFC. Thus, SCF, in combination with other growth factors, can generate large numbers of CFC from pre-CFC and appears to act earlier than hematopoietic growth factors described to date.