Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model

A. Schuh, A. Kroh, S. Konschalla, E. A. Liehn, R. M. Sobota, E. Al Biessen, I. Bot, S. T. Taha, A. Schober, N. Marx, C. Weber, A. Sasse

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Resumé

Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1a (SDF-1a) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1a-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1 alpha in infarcted myocardium. In addition, a significant increased density of CD31+ vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.
OriginalsprogEngelsk
TidsskriftJournal of Cellular and Molecular Medicine
Vol/bind16
Udgave nummer10
Sider (fra-til)2311-2320
Antal sider10
ISSN1582-1838
DOI
StatusUdgivet - 2012

Citer dette

Schuh, A. ; Kroh, A. ; Konschalla, S. ; Liehn, E. A. ; Sobota, R. M. ; Al Biessen, E. ; Bot, I. ; Taha, S. T. ; Schober, A. ; Marx, N. ; Weber, C. ; Sasse, A. / Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model. I: Journal of Cellular and Molecular Medicine. 2012 ; Bind 16, Nr. 10. s. 2311-2320.
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title = "Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model",
abstract = "Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1a (SDF-1a) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1a-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1 alpha in infarcted myocardium. In addition, a significant increased density of CD31+ vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.",
author = "A. Schuh and A. Kroh and S. Konschalla and Liehn, {E. A.} and Sobota, {R. M.} and {Al Biessen}, E. and I. Bot and Taha, {S. T.} and A. Schober and N. Marx and C. Weber and A. Sasse",
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Schuh, A, Kroh, A, Konschalla, S, Liehn, EA, Sobota, RM, Al Biessen, E, Bot, I, Taha, ST, Schober, A, Marx, N, Weber, C & Sasse, A 2012, 'Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model', Journal of Cellular and Molecular Medicine, bind 16, nr. 10, s. 2311-2320. https://doi.org/10.1111/j.1582-4934.2012.01539.x

Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model. / Schuh, A.; Kroh, A.; Konschalla, S.; Liehn, E. A.; Sobota, R. M.; Al Biessen, E.; Bot, I.; Taha, S. T.; Schober, A.; Marx, N.; Weber, C.; Sasse, A.

I: Journal of Cellular and Molecular Medicine, Bind 16, Nr. 10, 2012, s. 2311-2320.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model

AU - Schuh, A.

AU - Kroh, A.

AU - Konschalla, S.

AU - Liehn, E. A.

AU - Sobota, R. M.

AU - Al Biessen, E.

AU - Bot, I.

AU - Taha, S. T.

AU - Schober, A.

AU - Marx, N.

AU - Weber, C.

AU - Sasse, A.

PY - 2012

Y1 - 2012

N2 - Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1a (SDF-1a) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1a-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1 alpha in infarcted myocardium. In addition, a significant increased density of CD31+ vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.

AB - Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1a (SDF-1a) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1a-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1 alpha in infarcted myocardium. In addition, a significant increased density of CD31+ vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.

U2 - 10.1111/j.1582-4934.2012.01539.x

DO - 10.1111/j.1582-4934.2012.01539.x

M3 - Journal article

C2 - 22288686

VL - 16

SP - 2311

EP - 2320

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 10

ER -