Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization

Qin, Gangjian; Masaaki,; Silver, Marcy; Wecker, Andrea; Bord, Evelyn; Ma, Hong; Gavin, Mary; Goukassian, David A.; Yoon, Young Sup; Papayannopoulou, Thalia; Asahara, Takayuki; Kearney, Marianne; Thorne, Tina; Curry, Cynthia J.; Eaton, Liz; Heyd, Lindsay; Dinesh, Deepika; Kishore, Raj; Zhu, Yan; Losordo, Douglas W.

doi:10.1084/jem.20050459

Cited by 104 publications

(116 citation statements)

References 67 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…Of note, our results did not show a statistically significant difference after CD49d was blocked with antibodies before injection. Consistent with our finding, a recent study shows that blockade of CD49d in endothelial progenitor cells does not affect their homing and engraftment into ischemic sites in MI hearts or ischemic limbs (Qin et al, 2006).…”

Section: Discussionsupporting

confidence: 81%

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Huang

et al. 2007

MBoC

213

143

View full text Add to dashboard Cite

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. INTRODUCTIONCardiac repair and remodeling after ischemic injury involves myocyte hypertrophy, collagen deposition, and possibly ventricular dilatation (Sutton and Sharpe, 2000). Recent provocative data suggest that stem cells, either resident in the heart or originating from the bone marrow, may play an important role in the repair and regeneration of the injured myocardium (Anversa and Nadal-Ginard, 2002). We and others have shown that intramyocardial transplantation of bone marrow-derived stem cells (BMSCs) can promote cardiac repair with resulting functional improvement and reduced infarct size (Kocher et al., 2001;Mangi et al., 2003;Amado et al., 2005). In addition to direct transplantation, mobilization of BMSCs with cytokines such as granulocytecolony stimulating factor (G-CSF) and stem cell factor has been reported to enhance myocardial repair and improve cardiac function (Anversa and Nadal-Ginard, 2002;Askari et al., 2003). However, in a recent trial, the subcutaneous administration of G-CSF after acute myocardial infarction (MI) did not lead to further improvement in ventricular function compared with conventional treatment (Ripa et al., 2006). These controversial findings suggest the need to understand the molecular mechanisms involved with stem cell migration and engraftment into the infarcted myocardium.It has been reported that hematopoietic stem cells (HSCs) migrate in response to stromal-derived factor (SDF)-1␣, the ligand for the CXC chemokine receptor 4 (CXCR4) (Wright et al., 2002), and the up-regulation of SDF-1 in the ischemic myocardium mediates homing of HSCs vi...

show abstract

Section: Discussionsupporting

confidence: 81%

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Huang

et al. 2007

MBoC

213

143

View full text Add to dashboard Cite

show abstract

“…Therefore, CPC sheet transplantation may induce migration of bone marrow-derived cells to the infarcted heart, thereby improving cardiac function. Recently, anti-α 4 integrin Ab treatment was shown to improve cardiac function 2 weeks after MI by inhibiting interactions between bone marrow cells and their niches and promoting bone marrow cell migration and vasculogenesis (43). In the present study, anti-VLA-4 Ab treatment significantly attenuated improved cardiac function and angiogenesis following CPC sheet transplantation.…”

Section: Discussionsupporting

confidence: 49%

Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice

Matsuura¹,

Honda²,

Nagai³

et al. 2009

J. Clin. Invest.

157

195

View full text Add to dashboard Cite

“…After thoracotomy at the left 4 th or 5 th intercostal space, the LAD was ligated just distal to the bifurcation of the diagonal branch using 8.0 polypropylene sutures through a dissecting microscope (Qin et al, 2006;Cho et al, 2007). The apex of the left ventricle (LV) was observed for evidence of myocardial blanching and akinesia indicating interruption of coronary flow.…”

Section: Animals and Model Of Myocardial Infarctionmentioning

confidence: 99%

Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction

Park

Yoon

et al. 2011

Exp Mol Med

View full text Add to dashboard Cite

Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2-to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P ＜ 0.05), VEGF-D (6.1 fold, P ＜ 0.05), Lyve-1 (15 fold, P ＜ 0.05), and Prox-1 (11 fold, P ＜ 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P ＜ 0.01) and LV fractional shortening was higher in the EPC group accordingly (P ＜ 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.

show abstract

Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization

Cited by 104 publications

References 67 publications

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice

Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction

Contact Info

Product

Resources

About