CXCR4 positive bone mesenchymal stem cells migrate to human endothelial cell stimulated by ox-LDL via SDF-1alpha/CXCR4 signaling axis.
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.
Li
Mincai
M
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Yu
Jun
J
Li
Yan
Y
Li
Dujuan
D
Yan
Dan
D
Qu
Zhiling
Z
Ruan
Qiurong
Q
D001842:Bone and Bones / Q000502:physiology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014471:Umbilical Veins
C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D017931:DNA Primers; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D012313:RNA