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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism
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Cell Line
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Cells, Cultured
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Chemokine CXCL12
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Chemokines, CXC / genetics*
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Cyclophosphamide / pharmacology
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DNA Damage*
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Dose-Response Relationship, Radiation
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Endothelium, Vascular / cytology
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Endothelium, Vascular / metabolism
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Flow Cytometry
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Fluorouracil / pharmacology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / radiation effects
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, SCID
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Osteoblasts / cytology
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Osteoblasts / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Stem Cells / cytology
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Stem Cells / metabolism*
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Tumor Cells, Cultured
Substances
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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Cxcl12 protein, mouse
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RNA, Messenger
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Cyclophosphamide
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Fluorouracil