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

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

doi:10.1016/j.biomaterials.2014.02.028

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

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

^*Corresponding author for this work

Surgery, Cardiac Surgery Division

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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 invivo. 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.

Original language	English (US)
Pages (from-to)	4749-4758
Number of pages	10
Journal	Biomaterials
Volume	35
Issue number	17
DOIs	https://doi.org/10.1016/j.biomaterials.2014.02.028
State	Published - Jun 2014

Keywords

Angiogenesis
Cell therapy
Collagen
Integrins
Myocardial infarction
Regeneration

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2014.02.028

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Ahmadi, A., McNeill, B., Vulesevic, B., Kordos, M., Mesana, L., Thorn, S., Renaud, J. M., Manthorp, E., Kuraitis, D., Toeg, H. D., Mesana, T. G., Davis, D. R., Beanlands, R. S., DaSilva, J. N., deKemp, R. A., Ruel, M., & Suuronen, E. J. (2014). The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium. Biomaterials, 35(17), 4749-4758. https://doi.org/10.1016/j.biomaterials.2014.02.028

Ahmadi, Ali ; McNeill, Brian ; Vulesevic, Branka ; Kordos, Myra ; Mesana, Laura ; Thorn, Stephanie ; Renaud, Jennifer M. ; Manthorp, Emily ; Kuraitis, Drew ; Toeg, Hadi Daood ; Mesana, Thierry G. ; Davis, Darryl R. ; Beanlands, Rob S. ; DaSilva, Jean N. ; deKemp, Robert A. ; Ruel, Marc ; Suuronen, Erik J. / The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium. In: Biomaterials. 2014 ; Vol. 35, No. 17. pp. 4749-4758.

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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 invivo. 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",

author = "Ali Ahmadi and Brian McNeill and Branka Vulesevic and Myra Kordos and Laura Mesana and Stephanie Thorn and Renaud, {Jennifer M.} and Emily Manthorp and Drew Kuraitis and Toeg, {Hadi Daood} and Mesana, {Thierry G.} and Davis, {Darryl R.} and Beanlands, {Rob S.} and DaSilva, {Jean N.} and deKemp, {Robert A.} and Marc Ruel and Suuronen, {Erik J.}",

note = "Funding Information: We thank Suzanne Crowe, Rick Seymour, Gregory Cron, Tayebeh Hadizad, Tanja Sofrenovic, and C{\'e}line Giordano for technical assistance with this work. Support came from the Canadian Institutes of Health Research (CIHR; grant MOP-77536 to MR and EJS), the Heart & Stroke Foundation of Ontario (HSFO; program grant, PRG 6242 to RSB; and grant-in-aid T6793 to EJS) and the Ottawa Heart Institute Cardiac Surgery Endowed Chair (to MR). RSB is a Career Investigator of the HSFO. BM was the recipient of the Ottawa Heart Institute Lawrence Soloway Research Fellowship, BV, ST and DK were supported by Canadian Graduate Scholarships from the CIHR. ",

year = "2014",

month = jun,

doi = "10.1016/j.biomaterials.2014.02.028",

language = "English (US)",

volume = "35",

pages = "4749--4758",

journal = "Biomaterials",

issn = "0142-9612",

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Ahmadi, A, McNeill, B, Vulesevic, B, Kordos, M, Mesana, L, Thorn, S, Renaud, JM, Manthorp, E, Kuraitis, D, Toeg, HD, Mesana, TG, Davis, DR, Beanlands, RS, DaSilva, JN, deKemp, RA, Ruel, M & Suuronen, EJ 2014, 'The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium', Biomaterials, vol. 35, no. 17, pp. 4749-4758. https://doi.org/10.1016/j.biomaterials.2014.02.028

The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium. / Ahmadi, Ali; McNeill, Brian; Vulesevic, Branka; Kordos, Myra; Mesana, Laura; Thorn, Stephanie; Renaud, Jennifer M.; Manthorp, Emily; Kuraitis, Drew; Toeg, Hadi Daood; Mesana, Thierry G.; Davis, Darryl R.; Beanlands, Rob S.; DaSilva, Jean N.; deKemp, Robert A.; Ruel, Marc; Suuronen, Erik J.

In: Biomaterials, Vol. 35, No. 17, 06.2014, p. 4749-4758.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium

AU - Ahmadi, Ali

AU - McNeill, Brian

AU - Vulesevic, Branka

AU - Kordos, Myra

AU - Mesana, Laura

AU - Thorn, Stephanie

AU - Renaud, Jennifer M.

AU - Manthorp, Emily

AU - Kuraitis, Drew

AU - Toeg, Hadi Daood

AU - Mesana, Thierry G.

AU - Davis, Darryl R.

AU - Beanlands, Rob S.

AU - DaSilva, Jean N.

AU - deKemp, Robert A.

AU - Ruel, Marc

AU - Suuronen, Erik J.

N1 - Funding Information: We thank Suzanne Crowe, Rick Seymour, Gregory Cron, Tayebeh Hadizad, Tanja Sofrenovic, and Céline Giordano for technical assistance with this work. Support came from the Canadian Institutes of Health Research (CIHR; grant MOP-77536 to MR and EJS), the Heart & Stroke Foundation of Ontario (HSFO; program grant, PRG 6242 to RSB; and grant-in-aid T6793 to EJS) and the Ottawa Heart Institute Cardiac Surgery Endowed Chair (to MR). RSB is a Career Investigator of the HSFO. BM was the recipient of the Ottawa Heart Institute Lawrence Soloway Research Fellowship, BV, ST and DK were supported by Canadian Graduate Scholarships from the CIHR.

PY - 2014/6

Y1 - 2014/6

N2 - 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 invivo. 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.

AB - 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 invivo. 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.

KW - Angiogenesis

KW - Cell therapy

KW - Collagen

KW - Integrins

KW - Myocardial infarction

KW - Regeneration

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AN - SCOPUS:84896489047

VL - 35

SP - 4749

EP - 4758

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 17

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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