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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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Pressure-Volume loop analysis.Left ventricular pressure-volume analysis in the four groups 4 weeks post infarction. The CPC treated group exhibited preservation of ventricular volume in diastole (a) (p<0.01). An improved relaxation constant (Tau-Weiss) is observed in CPC treated mice (c) (p<0.01). (dP/dt)max (b) and preload recruitable stroke work (PRSW) (d) was improved in the CPC treated group exhibiting preserved contractility parameters. (e) Sample Pressure-volume loop recordings from individual mice four weeks after myocardial infarction. While the sham treated mouse has kept its end-diastolic and end-systolic volumes these parameters have increased in MI ones with less maximum pressure, however the degree of dilatation and remodeling seems increased in the saline treated mouse as compared to the one receiving CPCs.
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pone-0011536-g007: Pressure-Volume loop analysis.Left ventricular pressure-volume analysis in the four groups 4 weeks post infarction. The CPC treated group exhibited preservation of ventricular volume in diastole (a) (p<0.01). An improved relaxation constant (Tau-Weiss) is observed in CPC treated mice (c) (p<0.01). (dP/dt)max (b) and preload recruitable stroke work (PRSW) (d) was improved in the CPC treated group exhibiting preserved contractility parameters. (e) Sample Pressure-volume loop recordings from individual mice four weeks after myocardial infarction. While the sham treated mouse has kept its end-diastolic and end-systolic volumes these parameters have increased in MI ones with less maximum pressure, however the degree of dilatation and remodeling seems increased in the saline treated mouse as compared to the one receiving CPCs.

Mentions: In order to further access the cardiac functional capacity of the four animal groups we performed Pressure-Volume loop analysis (Fig. 7) [21]. Consistent with the echocardiographic analysis of ventricular dilatation, the end diastolic volume (EDV, Fig. 7a) for the saline-injected infracted animals measured 49.5±10.0 µl, as compared to 29.4±2.9 µl for the CPC-treated infracted animal group. The animals that underwent sham surgery and received either cells or saline injections measured 20.1±1.2 µl and 22.5±1.9 µl respectively.


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)

Pressure-Volume loop analysis.Left ventricular pressure-volume analysis in the four groups 4 weeks post infarction. The CPC treated group exhibited preservation of ventricular volume in diastole (a) (p<0.01). An improved relaxation constant (Tau-Weiss) is observed in CPC treated mice (c) (p<0.01). (dP/dt)max (b) and preload recruitable stroke work (PRSW) (d) was improved in the CPC treated group exhibiting preserved contractility parameters. (e) Sample Pressure-volume loop recordings from individual mice four weeks after myocardial infarction. While the sham treated mouse has kept its end-diastolic and end-systolic volumes these parameters have increased in MI ones with less maximum pressure, however the degree of dilatation and remodeling seems increased in the saline treated mouse as compared to the one receiving CPCs.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0011536-g007: Pressure-Volume loop analysis.Left ventricular pressure-volume analysis in the four groups 4 weeks post infarction. The CPC treated group exhibited preservation of ventricular volume in diastole (a) (p<0.01). An improved relaxation constant (Tau-Weiss) is observed in CPC treated mice (c) (p<0.01). (dP/dt)max (b) and preload recruitable stroke work (PRSW) (d) was improved in the CPC treated group exhibiting preserved contractility parameters. (e) Sample Pressure-volume loop recordings from individual mice four weeks after myocardial infarction. While the sham treated mouse has kept its end-diastolic and end-systolic volumes these parameters have increased in MI ones with less maximum pressure, however the degree of dilatation and remodeling seems increased in the saline treated mouse as compared to the one receiving CPCs.
Mentions: In order to further access the cardiac functional capacity of the four animal groups we performed Pressure-Volume loop analysis (Fig. 7) [21]. Consistent with the echocardiographic analysis of ventricular dilatation, the end diastolic volume (EDV, Fig. 7a) for the saline-injected infracted animals measured 49.5±10.0 µl, as compared to 29.4±2.9 µl for the CPC-treated infracted animal group. The animals that underwent sham surgery and received either cells or saline injections measured 20.1±1.2 µl and 22.5±1.9 µl respectively.

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