CHEMOKINES, CYTOKINES, AND INTERLEUKINS Reduced retention of radioprotective hematopoietic cells within the bone marrow microenvironment in CXCR4 / chimeric mice

The physiologic role of CXCR4 on hematopoietic stem/progenitor cells (HSPCs) is not fully understood. Here, we show that radioprotection of lethally irradiated mice by embryonic day 14.5 (E14.5) CXCR4 / fetal liver (FL) cells was markedly impaired when compared with CXCR4 / counterparts, but this defect was rescued when hosts were engrafted with high cell numbers. This quantitative defect contrasted with a similar content in hematopoietic colony-forming cells (CFCs), splenic colony-forming units (CFUs-S), and Lin Sca-1 c-kit cells in E14.5 CXCR4 / and CXCR4 / livers. In addition, the homing of HSPCs in the bone marrow was not altered as detected with a CFSE-staining assay. In contrast, a 30-fold increase in CFCs was seen in the circulation of mice stably reconstituted with CXCR4 / FL cells and this increment was already observed before hematopoiesis had reached a steady-state level. Together, the data strongly suggest that impaired retention may, at least in shortterm hematopoietic reconstitution, lead to a diminution in the number of available progenitors required for radioprotection. (Blood. 2006;107:2243-2251)