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 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.
Ponomaryov
T
T
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Peled
A
A
Petit
I
I
Taichman
R S
RS
Habler
L
L
Sandbank
J
J
Arenzana-Seisdedos
F
F
Magerus
A
A
Caruz
A
A
Fujii
N
N
Nagler
A
A
Lahav
M
M
Szyper-Kravitz
M
M
Zipori
D
D
Lapidot
T
T
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D003520:Cyclophosphamide / Q000494:pharmacology; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D003520:Cyclophosphamide; D005472:Fluorouracil