期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 73, 期 5, 页码 630-638出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.1002495
关键词
hematopoietic progenitor and stem cells; chemokines; cytokines; apoptosis
资金
- NHLBI NIH HHS [R01 HL67384, P60 HL53586, R01 HL56416, R01 HL63219] Funding Source: Medline
- NIDDK NIH HHS [T32 DK07519, R01 DK53674] Funding Source: Medline
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-crythroid, and CFU-granulocyte-crythroid-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.
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