Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and Gαi proteins and enhances engraftment of competitive, repopulating stem cells

Hal E. Broxmeyer, Lisa Kohli, Chang H. Kim, Younghee Lee, Charlie Mantel, Scott Cooper, Giao Hangoc, Montaser Shaheen, Xiaxin Li, D. Wade Clapp

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Stromal cell-derived factor-1 (SDF-1/CXCL12) enhances survival of myeloid progenitor cells. The two main questions addressed by us were whether these effects on the progenitors were direct-acting and if SDF-1/CXCL12 enhanced engrafting capability of competitive, repopulating mouse stem cells subjected to short-term ex vivo culture with other growth factors. SDF-1/CXCL12 had survival-enhancing/antiapoptosis effects on human bone marrow (BM) and cord blood (CB) and mouse BM colony-forming units (CFU)-granulocyte macrophage, burst-forming units-erythroid, and CFU-granulocyte-erythroid-macrophage-megakaryocyte with similar dose responses. The survival effects were direct-acting, as assessed on colony formation by single isolated human BM and CB CD34+++ cells. Effects were mediated through CXCR4 and God proteins. Moreover, SDF-1/CXCL12 greatly enhanced the engrafting capability of mouse long-term, marrow-competitive, repopulating stem cells cultured ex vivo with interleukin-6 and steel factor for 48 h. These results extend information on the survival effects mediated through the SDF-1/CXCL12-CXCR4 axis and may be of relevance for ex vivo expansion and gene-transduction procedures.

Original languageEnglish (US)
Pages (from-to)630-638
Number of pages9
JournalJournal of Leukocyte Biology
Volume73
Issue number5
DOIs
StatePublished - May 1 2003

Fingerprint

Myeloid Progenitor Cells
Chemokine CXCL12
Stem Cells
Bone Marrow
Survival
Fetal Blood
Proteins
Granulocyte-Macrophage Progenitor Cells
Stem Cell Factor
Interleukin-6
Blood Cells
Intercellular Signaling Peptides and Proteins
Genes

Keywords

  • Apoptosis
  • Chemokines
  • Cytokines
  • Hematopoietic progenitor and stem cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

Stromal cell-derived factor-1/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and Gαi proteins and enhances engraftment of competitive, repopulating stem cells. / Broxmeyer, Hal E.; Kohli, Lisa; Kim, Chang H.; Lee, Younghee; Mantel, Charlie; Cooper, Scott; Hangoc, Giao; Shaheen, Montaser; Li, Xiaxin; Clapp, D. Wade.

In: Journal of Leukocyte Biology, Vol. 73, No. 5, 01.05.2003, p. 630-638.

Research output: Contribution to journalArticle

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