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

Biomaterials. 2014 Jun;35(17):4749-58. doi: 10.1016/j.biomaterials.2014.02.028. Epub 2014 Mar 14.

Abstract

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 α2β1 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 α5 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 α2β1 and α5 integrin signaling mechanisms, rather than simply delivering the cells.

Keywords: Angiogenesis; Cell therapy; Collagen; Integrins; Myocardial infarction; Regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / metabolism*
  • Cell Survival / drug effects
  • Cell- and Tissue-Based Therapy
  • Cells, Cultured
  • Collagen / metabolism*
  • Heart / physiopathology
  • Humans
  • Integrin alpha2 / metabolism*
  • Integrin alpha2beta1 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / transplantation*
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Myocardium / pathology*
  • Neovascularization, Physiologic
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • Biocompatible Materials
  • Integrin alpha2
  • Integrin alpha2beta1
  • Collagen
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases