CXCR4 positive bone mesenchymal stem cells migrate to human endothelial cell stimulated by ox-LDL via SDF-1alpha/CXCR4 signaling axis

Exp Mol Pathol. 2010 Apr;88(2):250-5. doi: 10.1016/j.yexmp.2009.12.001. Epub 2009 Dec 16.

Abstract

Background: Bone mesenchymal stem cells (BMSCs) are attractive candidates for cell based therapies to cardiovascular disease such as infarction and atherosclerosis; however, the mechanisms responsible for stem cell chemotaxis and homing remain unknown. Chemokine stromal cell-derived factor 1 (SDF-1alpha) is involved in the process of atherogenesis. This study was aimed at investigating whether the SDF-1alpha of human umbilical vein endothelial cells (HUVECs) plays a role in migration of BM-derived CXCR4(+)(receptor for SDF-1alpha) stem cells.

Methods: HUVECs were cultured from human umbilical cords and was treated with ox-LDL. The mRNA and protein expression of SDF-1alpha was detected in HUVECs. CXCR4(+)BMSCs from bone marrow were isolated and were tested by migration and adhesion assays.

Results: It was found that ox-LDL induced HUVECs to increase the mRNA and protein expression of SDF-1alpha. Ox-LDL increased the migratory and adhesion response of CXCR4(+)BMSCs. When the neutralizing SDF-1alpha antibody abrogated the secreted SDF-1alpha, the migration and adhesion response of CXCR4(+)BMSCs markedly decreased.

Conclusions: Our data indicated that the endothelial cells (ECs) stimulated by ox-LDL could increase the BMSCs migratory response via SDF-1alpha/CXCR4 signaling axis. These findings provide a new paradigm for biological effects of ox-LDL and have implications for novel stem cell therapeutic strategies for atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone and Bones / physiology
  • Cell Culture Techniques
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / physiology*
  • Chemotaxis / drug effects
  • Chemotaxis / physiology
  • DNA Primers
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • Receptors, CXCR4 / physiology*
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Umbilical Veins

Substances

  • CXCR4 protein, human
  • Chemokine CXCL12
  • DNA Primers
  • Lipoproteins, LDL
  • RNA, Messenger
  • Receptors, CXCR4
  • Recombinant Proteins
  • Thiobarbituric Acid Reactive Substances
  • oxidized low density lipoprotein
  • RNA