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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Wiley
2011-01-01
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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. |
format | Article |
id | doaj-art-0c51febe3a534a8692bd645299272db0 |
institution | Kabale University |
issn | 1687-966X 1687-9678 |
language | English |
publishDate | 2011-01-01 |
publisher | Wiley |
record_format | Article |
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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