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

Tanya Ponomaryov, Amnon Peled, Isabelle Petit, Russell S. Taichman, Liliana Habler, Judith Sandbank, Fernando Arenzana-Seisdedos, Aude Magerus, Antonio Caruz, Nobutaka Fujii, Arnon Nagler, Meir Lahav, Martin Szyper-Kravitz, Dov Zipori, Tsvee Lapidot*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 DNAdamaging 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.

Original languageEnglish
Pages (from-to)1331-1339
Number of pages9
JournalJournal of Clinical Investigation
Volume106
Issue number11
DOIs
StatePublished - 2000
Externally publishedYes

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