期刊
STEM CELLS
卷 32, 期 4, 页码 1043-1054出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.1624
关键词
Hematopoietic stem cell transplantation; Mobilization; Adult hematopoietic stem cells; NOD/SCID chimeras; Adhesion receptors
资金
- Inserm Avenir program
- Inca
- Association pour la Recherche contre le Cancer (ARC) [4981]
- Canceropole PACA
- Inserm
- DGOS (SIRIC label)
- Fondation pour la Recherche Medicale (FRM)
- Lilly Institute
- Inserm/Region
- ARC
The junctional adhesion molecules Jam-b and Jam-c interact together at interendothelial junctions and have been involved in the regulation of immune response, inflammation, and leukocyte migration. More recently, Jam-c has been found to be expressed by hematopoietic stem and progenitor cells (HSPC) in mouse. Conversely, we have reported that Jam-b is present on bone marrow stromal cells and that Jam-b-deficient mice have defects in the regulation of hematopoietic stem cell pool. In this study, we have addressed whether interaction between Jam-b and Jam-c participates to HSPC mobilization or hematopoietic reconstitution after irradiation. We show that a blocking monoclonal antibody directed against Jam-c inhibits hematopoietic reconstitution, progenitor homing to the bone marrow, and induces HSPC mobilization in a Jam-b dependent manner. In the latter setting, antibody treatment over a period of 3 days does not alter hematopoietic differentiation nor induce leukocytosis. Results are translated to human hematopoietic system in which a functional adhesive interaction between JAM-B and JAM-C is found between human HSPC and mesenchymal stem cells. Such an interaction does not occur between HSPC and human endothelial cells or osteoblasts. It is further shown that anti-JAM-C blocking antibody interferes with CD34(+) hematopoietic progenitor homing in mouse bone marrow suggesting that monoclonal antibodies inhibiting JAM-B/JAM-C interaction may represent valuable therapeutic tools to improve stem cell mobilization protocols. Stem Cells 2014;32:1043-1054
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