Zebrafish Cdh5 negatively regulates mobilization of aorta-gonad-mesonephros-derived hematopoietic stem cells

Establishment of a hematopoietic stem cell（HSC）pool depends on the appropriate formation,maturation and mobilization of HSCs in vertebrates.In mice,the aorta-gonad-mesonephros（AGM）is a prominent site for the formation of definitive HSCs from endothelial cells,although the placenta and yolk sac also give rise to HSCs（Mikkola and Orkin,2006;Chen et al.,2009）.After formation,AGM-derived HSCs migrate to the fetal liver（FL）,and ultimately to the bone marrow （BM）, two definitive hematopoietic organs （Cumano and Godin, 2007）.

Role of adhesion molecules in mobilization of hematopoietic cells

To study the changes of adhesion molecules' expressions during the recombinant h u man granulocyte colony stimulating factor (rhG CSF) mobilization in periphera l blood stem cell transplantation (PBSCT), and to confirm the influence of rhG CSF on hematopoietic stem cells, which are proposed to guide mobilization in PBS CT Methods Mice were injected subcutaneously with diluted rhG CSF or normal saline for 7 d ays The blood Sca 1 + stem cell count and bone marrow (BM) nucleated cell co unt were enumerated The expressions of CD49d and CD44 and the adhesive ability of mononuclear cells to bone marrow matrix (fibronectin) were examined by flow c ytometry and 51 Cr adhesive assay, respectively Results The mobilizing effect of rhG CSF on mice was the same as on humans The number of Sca 1 + cells in peripheral blood reached the peak on the seventh day, the BM nucleated cell count was reduced, and the expressions of CD49d and the cells ' adhesive ability in BM and PB declined Conclusions rhG CSF can reduce some cell adhesion molecules' expressions and the adhesive a bility of hematopoietic stem cells to BM matrix, therefore mobilizing hematopoie tic stem cells (HSC) from the BM to the peripheral blood

Negative association of donor age with CD34＋ cell dose in mixture allografts of G-CSF-primed bone marrow and G-CSF-mobilized peripheral blood harvests

Background The effects of donor characteristics on CD34＋ cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor （G-CSF）- primed bone marrow （G-BM） and G-CSF-mobilized peripheral blood （G-PB） were used. The aim of this study was to investigate the effects of donor characteristics on CD34＋ cell dose in mixture allografts of G-BM and G-PB. Methods A total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People＇s Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 pg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34＋ cell dose less than 2× 106 cells/kg recipient body weight was considered a poor mobilization. Results Of the 162 donors, 31 （19.1%） did not attain this threshold. The obtained median CD34＋ cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×106/kg, 2.40×106/kg, and 3.47×106/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34＋ cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index （BMI）, and weight. Conclusion Donor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34＋ cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34＋ cells for transplantation.