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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·2003·Journal of Leukocyte Biology
DOI 10.1189/jlb.1002495
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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 Gαi 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.

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Cited by

Metadata

Authors
Broxmeyer, H. E., Kohli, L., Kim, C. H., Lee, Y., Mantel, C., Cooper, S., Hangoc, G., Shaheen, M., Li, X., & Clapp, D. W.
Affiliations
  • Department of Microbiology/Immunology, Indiana University School of Medicine , Indianapolis
  • Laboratory of Immunology and Hematopoiesis, Department of Veterinary Pathology, Purdue University,   West Lafayette, Indiana
  • Department of Medicine (Hematoogy/Oncology), Indiana University School of Medicine , Indianapolis
  • Department of Pediatrics (Neonatology), Indiana University School of Medicine , Indianapolis
Venue
Journal of Leukocyte Biology
Publisher
Oxford University Press (OUP)
Published
2003-05-01
Volume
73
Issue
5
Pages
630-638
ISSN
  • 0741-5400
  • 1938-3673
DOI
10.1189/jlb.1002495
Cited by
162
References
0
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Funders
  • Public Health Service (RO1 HL56416, RO1 HL67384, RO1 DK53674, P60 HL53586, RO1 HL63219)
  • NIH (DK07519)

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