Steel factor influences the distribution and activity of murine hematopoietic stem cells in vivo

W. H. Fleming, E. J. Alpern, N. Uchida, K. Ikuta, I. L. Weissman

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

To determine the effects of steel factor (SIF) on the number and distribution of phenotypically defined hematopoietic stem cells in vivo, mice were treated with continuous s.c. infusions of SIF for up to 7 days. The bone marrow demonstrated a transient 5-fold increase in the number of c-kit- positive lineage-negative/low cells with no change in cellularity. The radioprotective capacity of bone marrow cells was significantly reduced, and a 30% decrease in Thy(lo) Lin(-/lo) Sca-1+ stem cells (Sca+ cells) was observed. In marked contrast, in the spleen a 2-fold increase in cellularity was accompanied by a 24-fold increase in c-kit-positive lineage-negative/low cells. SIF-treated spleen cells provided increased radioprotection and a corresponding 4-fold increase in the number of Sca+ cells. In the peripheral blood, an increase in both neutrophils and lymphocytes resulted; however, the number of c-kit-positive lineage-negative/low cells remained <1%. SIF produced a 25-fold increase in radioprotection capacity and a 20-fold increase in the number of Sca+ cells in the peripheral blood. The increased radioprotection capacity of both the spleen cells and peripheral blood cells was associated with donor-derived, long-term multilineage reconstitution of recipient mice. The total number of Sca+ cells isolated per mouse after SIF treatment was not significantly increased. These results show that exogenous SIF treatment causes a redistribution of Sca+ cells and stem cell activity while having little effect on the total number of stem cells in the mouse.

Original languageEnglish (US)
Pages (from-to)3760-3764
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number8
DOIs
StatePublished - Jan 1 1993

    Fingerprint

Keywords

  • bone marrow transplantation
  • growth factors
  • peripheral blood stem cells

ASJC Scopus subject areas

  • General

Cite this