Hematopoietic stem cell (HSC) transplants are used to treat various life-threatening conditions, including severe aplastic anemia, certain forms of cancer, and some inherited disorders of the immune system. When injected into the blood, HSCs make their way to the bone marrow (where hematopoiesis takes place in the adult); however, the mechanisms whereby they become established there have been unclear. Noting that HSCs reside close to the endosteal lining of the bone, where extracellular calcium concentration ([Ca2+]o) can reach 40 mM, Adams et al. investigated the possibility that HSCs might be sensitive to [Ca2+]o.The authors used flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) to show that a stem-cell-enriched population of bone marrow cells expressed CaR, a G protein-coupled receptor that detects [Ca2+]o. The bone marrow of 3-day-old mice lacking CaR contained reduced numbers of cells; moreover, phenotypic and functional assays indicated that, whereas primitive hematopoietic cells were present in the blood and spleen of CaR–/– mice, their numbers were reduced in bone marrow. Fetal hematopoiesis takes place in the liver, and HSCs from the liver of CaR–/– fetal mice were comparable to those of wild-type mice. Moreover, primitive fetal liver hematopoietic cells from CaR–/– mice homed to the bone marrow of wild-type mice and migrated up a stromal cell-derived factor-α gradient. However, they adhered poorly to collagen I compared with cells from wild-type mice, failed to lodge in the endosteal niche, and engrafted poorly when competing with wild-type stem cells. Thus, the authors conclude that calcium sensing by the CaR plays a key role in the engraftment of HSCs in the bone marrow.
G. B. Adams, K. T. Chabner, I. R. Alley, D. P. Olson, Z. M. Szczepiorkowski, M. C. Poznansky, C. H. Kos, M. R. Pollak, E. M. Brown, D. T. Scadden, Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439, 599-603 (2006). [PubMed]