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Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

Christoforou N, Oskouei BN, Esteso P, Hill CM, Zimmet JM, Bian W, Bursac N, Leong KW, Hare JM, Gearhart JD - PLoS ONE (2010)

Bottom Line: Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances.Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function.Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina, United States of America. nc28@duke.edu

ABSTRACT
Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

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Electromechanical coupling capacity of CPCs.Electrical and mechanical coupling of differentiated CPCs with the host myocardium and neonatal rat ventricular myocytes. β-Galactosidase(+) cardiomyocytes form gap junctions as demonstrated by Connexin 43 immunostaining within the infarcted region (a, c), as well as in the healthy myocardium (b), and at the border area between healthy and infarcted myocardium (d). CPCs differentiate in vitro into GFP(+)/α-Actinin(+) cardiomyocytes (e) and mechanically couple with co-cultured neonatal rat ventricular myocytes as determined by N-Cadherin detection at the border region between the two cell types (f).
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pone-0011536-g005: Electromechanical coupling capacity of CPCs.Electrical and mechanical coupling of differentiated CPCs with the host myocardium and neonatal rat ventricular myocytes. β-Galactosidase(+) cardiomyocytes form gap junctions as demonstrated by Connexin 43 immunostaining within the infarcted region (a, c), as well as in the healthy myocardium (b), and at the border area between healthy and infarcted myocardium (d). CPCs differentiate in vitro into GFP(+)/α-Actinin(+) cardiomyocytes (e) and mechanically couple with co-cultured neonatal rat ventricular myocytes as determined by N-Cadherin detection at the border region between the two cell types (f).

Mentions: The capacity of the differentiated CPCs to electrocouple in vivo with the host myocardium was examined by immunohistochemical analysis (Figs. 5a–d). The majority of the βGal(+) cardiomyocytes which also exhibited Connexin 43 gap-junction staining were detected at the site of the infarct (Figs. 5a, c). A small number of the donor cells were detected within the healthy myocardium (Fig. 5b) or at the border between healthy tissue and infarct (Fig. 5d).


Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

Christoforou N, Oskouei BN, Esteso P, Hill CM, Zimmet JM, Bian W, Bursac N, Leong KW, Hare JM, Gearhart JD - PLoS ONE (2010)

Electromechanical coupling capacity of CPCs.Electrical and mechanical coupling of differentiated CPCs with the host myocardium and neonatal rat ventricular myocytes. β-Galactosidase(+) cardiomyocytes form gap junctions as demonstrated by Connexin 43 immunostaining within the infarcted region (a, c), as well as in the healthy myocardium (b), and at the border area between healthy and infarcted myocardium (d). CPCs differentiate in vitro into GFP(+)/α-Actinin(+) cardiomyocytes (e) and mechanically couple with co-cultured neonatal rat ventricular myocytes as determined by N-Cadherin detection at the border region between the two cell types (f).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902505&req=5

pone-0011536-g005: Electromechanical coupling capacity of CPCs.Electrical and mechanical coupling of differentiated CPCs with the host myocardium and neonatal rat ventricular myocytes. β-Galactosidase(+) cardiomyocytes form gap junctions as demonstrated by Connexin 43 immunostaining within the infarcted region (a, c), as well as in the healthy myocardium (b), and at the border area between healthy and infarcted myocardium (d). CPCs differentiate in vitro into GFP(+)/α-Actinin(+) cardiomyocytes (e) and mechanically couple with co-cultured neonatal rat ventricular myocytes as determined by N-Cadherin detection at the border region between the two cell types (f).
Mentions: The capacity of the differentiated CPCs to electrocouple in vivo with the host myocardium was examined by immunohistochemical analysis (Figs. 5a–d). The majority of the βGal(+) cardiomyocytes which also exhibited Connexin 43 gap-junction staining were detected at the site of the infarct (Figs. 5a, c). A small number of the donor cells were detected within the healthy myocardium (Fig. 5b) or at the border between healthy tissue and infarct (Fig. 5d).

Bottom Line: Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances.Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function.Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina, United States of America. nc28@duke.edu

ABSTRACT
Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

Show MeSH
Related in: MedlinePlus