Reduced Retention of Radioprotective Hematopoietic Cells Within the Bone Marrow Microenvironment in Cxcr4-/- Chimeric Mice.
From: INSERM U362, IFR54, Institut Gustave Roussy, Villejuif Cedex, France.
Blood
- Publish Date: Mar 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 6
- Pages: 2243-51
- Medium: Print
- Language: English
- Citation (JAMA): Foudi Adlen, Jarrier Peggy, Zhang Yanyan, et al. Reduced Retention of Radioprotective Hematopoietic Cells Within the Bone Marrow Microenvironment in Cxcr4-/- Chimeric Mice.. Blood Mar 2006;107:2243-51
Abstract
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 short-term hematopoietic reconstitution, lead to a diminution in the number of available progenitors required for radioprotection.
Mesh Headings (Keywords): Animals, Bone Marrow, Cell Movement, Embryo, Mammalian, Hematopoiesis, Hematopoietic Stem Cells, Liver, Mice, Mice, Knockout, Mice, Transgenic, Receptors, CXCR4, Spleen, Whole-Body Irradiation
Check for Full Text / PubMed Unique Identifier (PMID): 16291599
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