The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium

被引：29

作者：

Ahmadi, Ali ^{[1
,2
]}

McNeill, Brian ^{[1
,2
]}

Vulesevic, Branka ^{[1
,2
]}

Kordos, Myra ^{[2
,3
]}

Mesana, Laura ^{[1
]}

Thorn, Stephanie ^{[2
,3
]}

Renaud, Jennifer M. ^{[2
,3
]}

Manthorp, Emily ^{[1
,2
]}

Kuraitis, Drew ^{[1
,2
]}

Toeg, Hadi ^{[1
,2
]}

Mesana, Thierry G. ^{[1
]}

Davis, Darryl R. ^{[4
]}

Beanlands, Rob S. ^{[2
,3
,4
]}

DaSilva, Jean N. ^{[2
,3
]}

deKemp, Robert A. ^{[2
,3
]}

Ruel, Marc ^{[1
,2
]}

Suuronen, Erik J. ^{[1
,2
]}

机构：

[1] Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7, Canada

[2] Univ Ottawa, Inst Heart, Mol Funct & Imaging Program, Ottawa, ON K1Y 4W7, Canada

[3] Univ Ottawa, Inst Heart, Cardiac PET Ctr, Ottawa, ON K1Y 4W7, Canada

[4] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON K1Y 4W7, Canada

来源：

BIOMATERIALS | 2014年 / 35卷 / 17期

基金：

加拿大健康研究院;

关键词：

Angiogenesis; Cell therapy; Collagen; Integrins; Myocardial infarction; Regeneration; ENDOTHELIAL PROGENITOR CELLS; VENTRICULAR-FUNCTION; LINKED KINASE; STEM-CELLS; IN-VIVO; PROMOTES; ADHESION; DIFFERENTIATION; TRANSPLANTATION; VASCULOGENESIS;

D O I：

10.1016/j.biomaterials.2014.02.028

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

Injectable delivery matrices hold promise in enhancing engraftment and the overall efficacy of cardiac cell therapies; however, the mechanisms responsible remain largely unknown. Here we studied the interaction of a collagen matrix with circulating angiogenic cells (CACs) in a mouse myocardial infarction model. CACs + matrix treatment enhanced CAC engraftment, and improved myocardial perfusion, viability and function compared to cells or matrix alone. Integrin-linked kinase (ILK) was up-regulated in matrix-cultured CACs. Integrin alpha 2 beta 1 blocking prevented ILK up-regulation, significantly reduced the adhesion, proliferation, and paracrine properties of matrix-cultured CACs, and negated the benefits of CACs + matrix therapy in vivo. Furthermore, integrin alpha 5 was essential for the angiogenic potential of CACs on matrix. These findings indicate that the synergistic therapeutic effect of CACs + matrix therapy in MI requires the matrix to enhance CAC function via alpha 2 beta 1 and alpha 5 integrin signaling mechanisms, rather than simply delivering the cells. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：4749 / 4758

页数：10

共 45 条

[1]

Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling [J].