Induction of the Chemokine Stromal-Derived factor-1 Following DNA Damage Improves Human Stem Cell Function

J Clin Invest. 2000 Dec;106(11):1331-9. doi: 10.1172/JCI10329.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / genetics*
  • Cyclophosphamide / pharmacology
  • DNA Damage*
  • Dose-Response Relationship, Radiation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Flow Cytometry
  • Fluorouracil / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / radiation effects
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tumor Cells, Cultured

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • RNA, Messenger
  • Cyclophosphamide
  • Fluorouracil