Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice - The role of SDF-1/CXCR4 interactions

被引：164
作者：
Lapidot, T [1 ]
机构：
[1] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
来源：
HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES | 2001年 / 938卷
关键词：
human stem cell; chemokine SDF-1; immune-deficient NOD/SCID mice;
D O I：
10.1111/j.1749-6632.2001.tb03577.x
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The mechanism of hematopoietic stem cell migration and repopulation is not fully understood. Murine fetuses that lack the chemokine stromal-derived factor one (SDF-1null) or its receptor CXCR4 (CXCR4null) have multiple defects that are lethal, including impaired bone marrow hematopoiesis. These results suggest a major role for SDF-1/CXCR4 interactions in murine stem cell homing from the fetal liver into the bone marrow and its repopulation during development. SDF-1 is highly conserved between different species. Human and murine SDF-1 are cross-reactive and differ in one amino acid. Recently, we reported that SDF-1 and CXCR4 are essential for homing and repopulation of humune-deficient NOD/SCID and B2mnull NOD/SCID mice by human stem cells. In addition, immature human CD34(+) cells and primitive CD34(+)/CD38(-/low) cells, which do not migrate toward a gradient of SDF-1 in vitro, and do not home and repopulate in vivo the murine bone marrow, can become functional repopulating cells by short-term 16-48 hr in vitro stimulation with cytokines such as SCF and IL-6 prior to transplantation. These cytokines increase surface CXCR4 expression, migration toward SDF-1, and in vivo homing and repopulation. We discuss the pleiotropic roles of SDF-1/CXCR4 interactions in human stem cell migration, development, and repopulation in transplanted immune-deficient mice.
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收藏
页码：83 / 95
页数：13
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