Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function
Tanya Ponomaryov, … , Dov Zipori, Tsvee Lapidot
Tanya Ponomaryov, … , Dov Zipori, Tsvee Lapidot
Published December 1, 2000
Citation Information: J Clin Invest. 2000;106(11):1331-1339. https://doi.org/10.1172/JCI10329.
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Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function

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.

Authors

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

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Increased homing of human CD45+ cells transplanted 48 hours after treatm...
Increased homing of human CD45+ cells transplanted 48 hours after treatment with TBI, Cy, or 5-FU. (a) FACS plots, CD45+: CB MNC, human CB MNC before transplantation; CTRL, nontransplanted murine BM; NT, transplantation of human CB MNC into nontreated mice; Irrad. 0 h, transplanted immediately after TBI; Irrad. 48 h, transplanted 48 hours after TBI; 5-FU or Cy, transplanted 48 hours after treatment. (b) Total numbers of human CD45+ cells in the murine BM and spleen, 24 hours after transplantation of human CB MNC (2 × 107/mouse) into nontreated (NT) or treated NOD/SCID mice. Results from two experiments, mean ± SE, are shown. Amounts of human cells were calculated for the total organ based on acquisition number of cells and cell numbers in the total organ. Numbers inside the chart represent P values calculated with Student’s t test. FL-1, anti-CD45 FITC; FL-2, internal fluorescence.