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

Ponomaryov, T; Peled, A; Petit, I; Taichman, R S; Habler, L; Sandbank, J; Arenzana-Seisdedos, F; Magerus, A et al. · J Clin Invest · 2000

basic_science · Level V

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Abstract

The chemokine stromal-derived factor-1 (SDF-1) controls many aspects of stem cell function. Details of its regulation and sites of production are currently unknown. We report that in the bone marrow, SDF-1 is produced mainly by immature osteoblasts and endothelial cells. Conditioning with DNA-damaging agents (ionizing irradiation, cyclophosphamide, and 5-fluorouracil) caused an increase in SDF-1 expression and in CXCR4-dependent homing and repopulation by human stem cells transplanted into NOD/SCID mice. Our findings suggest that immature osteoblasts and endothelial cells control stem cell homing, retention, and repopulation by secreting SDF-1, which also participates in host defense responses to DNA damage.

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