Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function

The chemokine stromal-derived factor-1 (SDF-1) controls many aspects of ste m cell function. Details of its regulation and sites of production are curr ently unknown. We report that in the bone marrow, SDF-1 is produced mainly by immature osteoblasts and endothelial cells. Conditioning with DNA-damagi ng agents (ionizing irradiation, cyclophosphamide, and 5-fluorouracil) caus ed an increase in SDF-1 expression and in CXCR4-dependent homing and repopu lation by human stem cells transplanted into NOD/SCID mice. Our findings su ggest that immature osteoblasts and endothelial cells control stem cell hom ing, retention, and repopulation by secreting SDF-1, which also participate s in host defense responses to DNA damage.