The role of integrin alpha 2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium

作者：Ahmadi Ali; McNeill Brian; Vulesevic Branka; Kordos Myra; Mesana Laura; Thorn Stephanie; Renaud Jennifer M; Manthorp Emily; Kuraitis Drew; Toeg Hadi; Mesana Thierry G; Davis Darryl R; Beanlands Rob S; DaSilva Jean N; deKemp Robert A; Ruel Marc; Suuronen Erik J^*

来源：Biomaterials, 2014, 35(17): 4749-4758.

DOI：10.1016/j.biomaterials.2014.02.028

• Angiogenesis
• Cell therapy
• Collagen
• Integrins
• Myocardial infarction
• Regeneration

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.

• 出版日期2014-6