Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration

Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardia...

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Main Authors: Kenneth R. Boheler, Robert N. Joodi, Hui Qiao, Ondrej Juhasz, Amanda L. Urick, Sandra L. Chuppa, Rebekah L. Gundry, Robert P. Wersto, Rong Zhou
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.4061/2011/214203
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author Kenneth R. Boheler
Robert N. Joodi
Hui Qiao
Ondrej Juhasz
Amanda L. Urick
Sandra L. Chuppa
Rebekah L. Gundry
Robert P. Wersto
Rong Zhou
author_facet Kenneth R. Boheler
Robert N. Joodi
Hui Qiao
Ondrej Juhasz
Amanda L. Urick
Sandra L. Chuppa
Rebekah L. Gundry
Robert P. Wersto
Rong Zhou
author_sort Kenneth R. Boheler
collection DOAJ
description Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.
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institution Kabale University
issn 1687-966X
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publishDate 2011-01-01
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series Stem Cells International
spelling doaj-art-0c51febe3a534a8692bd645299272db02025-02-03T01:00:10ZengWileyStem Cells International1687-966X1687-96782011-01-01201110.4061/2011/214203214203Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and RegenerationKenneth R. Boheler0Robert N. Joodi1Hui Qiao2Ondrej Juhasz3Amanda L. Urick4Sandra L. Chuppa5Rebekah L. Gundry6Robert P. Wersto7Rong Zhou8Molecular Cardiology and Stem Cell Unit, Laboratory of Cardiovascular Sciences, National Institute of Aging, NIH, Baltimore, MD 21224, USAUMDNJ-Robert Wood Johnson Medical School, One Cooper Plaza, Camden, NJ 08103, USALaboratories of Molecular Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USAMolecular Cardiology and Stem Cell Unit, Laboratory of Cardiovascular Sciences, National Institute of Aging, NIH, Baltimore, MD 21224, USADepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USADepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USADepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USAResource Research Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USALaboratories of Molecular Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USAPluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.http://dx.doi.org/10.4061/2011/214203
spellingShingle Kenneth R. Boheler
Robert N. Joodi
Hui Qiao
Ondrej Juhasz
Amanda L. Urick
Sandra L. Chuppa
Rebekah L. Gundry
Robert P. Wersto
Rong Zhou
Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration
Stem Cells International
title Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration
title_full Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration
title_fullStr Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration
title_full_unstemmed Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration
title_short Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration
title_sort embryonic stem cell derived cardiomyocyte heterogeneity and the isolation of immature and committed cells for cardiac remodeling and regeneration
url http://dx.doi.org/10.4061/2011/214203
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