title: The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium.
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.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmadi
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: McNeill
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Branka
authors.initials: B
authors.lastname: Vulesevic
authors.affiliation: Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Myra
authors.initials: M
authors.lastname: Kordos
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Mesana
authors.affiliation: Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Thorn
authors.affiliation: Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Renaud
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Manthorp
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Drew
authors.initials: D
authors.lastname: Kuraitis
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Hadi
authors.initials: H
authors.lastname: Toeg
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Mesana
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Darryl R
authors.initials: DR
authors.lastname: Davis
authors.affiliation: Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Rob S
authors.initials: RS
authors.lastname: Beanlands
authors.affiliation: Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Jean N
authors.initials: JN
authors.lastname: DaSilva
authors.affiliation: Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: deKemp
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Molecular Function and Imaging Program, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada. Electronic address: esuuronen@ottawaheart.ca.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism*; D038982:Integrin alpha2beta1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D001672:Biocompatible Materials; D003094:Collagen; D039421:Integrin alpha2; D038982:Integrin alpha2beta1; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: Angiogenesis; Cell therapy; Collagen; Integrins; Myocardial infarction; Regeneration