
<ArticleTitle>Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of <prot>SDF-1</prot>/<prot>CXCR4</prot> interactions.</ArticleTitle>
<AbstractText>The mechanism of hematopoietic stem cell migration and repopulation is not fully understood. Murine fetuses that lack the chemokine <prot>stromal-derived factor one</prot> (<prot>SDF-1</prot>null) or its receptor <prot>CXCR4</prot> (<prot>CXCR4</prot>null) have multiple defects that are lethal, including impaired bone marrow hematopoiesis. These results suggest a major role for <prot>SDF-1</prot>/<prot>CXCR4</prot> interactions in murine stem cell homing from the fetal liver into the bone marrow and its repopulation during development. <prot>SDF-1</prot> is highly conserved between different species. Human and murine <prot>SDF-1</prot> are cross-reactive and differ in one amino acid. Recently, we reported that <prot>SDF-1</prot> and <prot>CXCR4</prot> are essential for homing and repopulation of immune-deficient NOD/SCID and B2mnull NOD/SCID mice by human stem cells. In addition, immature human <prot>CD34</prot>+ cells and primitive <prot>CD34</prot>+/<prot>CD38</prot>-/low cells, which do not migrate toward a gradient of <prot>SDF-1</prot> 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 <prot>SCF</prot> and <prot>IL-6</prot> prior to transplantation. These cytokines increase surface <prot>CXCR4</prot> expression, migration toward <prot>SDF-1</prot>, and in vivo homing and repopulation. We discuss the pleiotropic roles of <prot>SDF-1</prot>/<prot>CXCR4</prot> interactions in human stem cell migration, development, and repopulation in transplanted immune-deficient mice.</AbstractText>
