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Vol. 18, Issue 8, 2873-2882, August 2007

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Mesenchymal Stem Cells Use Integrin 1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

James E. Ip^*,, Yaojiong Wu^*,,, Jing Huang, Lunan Zhang^*,, Richard E. Pratt^*,, and Victor J. Dzau^*,

Department of Medicine, Duke University School of Medicine, Durham, NC 27710; and *Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115

Submitted February 23, 2007; Revised April 23, 2007; Accepted May 8, 2007
Monitoring Editor: Richard Assoian

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 1, integrin 4, 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 1 blockade but not integrin 4 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.

These authors contributed equally to this work.

Address correspondence to: Victor J. Dzau (dzau{at}duke.edu).

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