Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for myocardial migration and engraftment.
Recent evidence has demonstrated the importance of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic myocardium are unknown. In this study, we developed a functional genomics approach toward the identification of mediators of engraftment and migration of BM-MSCs within the ischemic myocardium. Our strategy involves microarray profiling (>22,000 probes) of ischemic hearts, complemented by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting of corresponding adhesion molecule and cytokine receptors in BM-MSCs to focus on the coexpressed pairs only. Our data revealed nine complementary adhesion molecules and cytokine receptors, including integrin beta1, integrin alpha4, and CXC chemokine receptor 4 (CXCR4). To examine their functional contributions, we first blocked selectively these receptors by preincubation of BM-MSCs with specific neutralizing antibodies, and then we administered these cells intramyocardially. A significant reduction in the total number of BM-MSC in the infarcted myocardium was observed after integrin beta1 blockade but not integrin alpha4 or CXCR4 blockade. The latter observation is distinctively different from that reported for hematopoietic stem cells (HSCs). Thus, our data show that BM-MSCs use a different pathway from HSCs for intramyocardial trafficking and engraftment.
Ip
James E
JE
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Wu
Yaojiong
Y
Huang
Jing
J
Zhang
Lunan
L
Pratt
Richard E
RE
Dzau
Victor J
VJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D019012:Integrin beta1 / Q000378:metabolism*; D008024:Ligands; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000235:genetics; D009206:Myocardium / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
D000906:Antibodies; D019012:Integrin beta1; D008024:Ligands; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface