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Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy

The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and...

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Autores principales: Aratyn-Schaus, Yvonne, Pasqualini, Francesco S., Yuan, Hongyan, McCain, Megan L., Ye, George J.C., Sheehy, Sean P., Campbell, Patrick H., Parker, Kevin Kit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754718/
https://www.ncbi.nlm.nih.gov/pubmed/26858266
http://dx.doi.org/10.1083/jcb.201508026
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author Aratyn-Schaus, Yvonne
Pasqualini, Francesco S.
Yuan, Hongyan
McCain, Megan L.
Ye, George J.C.
Sheehy, Sean P.
Campbell, Patrick H.
Parker, Kevin Kit
author_facet Aratyn-Schaus, Yvonne
Pasqualini, Francesco S.
Yuan, Hongyan
McCain, Megan L.
Ye, George J.C.
Sheehy, Sean P.
Campbell, Patrick H.
Parker, Kevin Kit
author_sort Aratyn-Schaus, Yvonne
collection PubMed
description The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell–derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell–cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell–cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes.
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spelling pubmed-47547182016-08-15 Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy Aratyn-Schaus, Yvonne Pasqualini, Francesco S. Yuan, Hongyan McCain, Megan L. Ye, George J.C. Sheehy, Sean P. Campbell, Patrick H. Parker, Kevin Kit J Cell Biol Research Articles The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell–derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell–cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell–cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes. The Rockefeller University Press 2016-02-15 /pmc/articles/PMC4754718/ /pubmed/26858266 http://dx.doi.org/10.1083/jcb.201508026 Text en © 2016 Aratyn-Schaus et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Aratyn-Schaus, Yvonne
Pasqualini, Francesco S.
Yuan, Hongyan
McCain, Megan L.
Ye, George J.C.
Sheehy, Sean P.
Campbell, Patrick H.
Parker, Kevin Kit
Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
title Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
title_full Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
title_fullStr Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
title_full_unstemmed Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
title_short Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
title_sort coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754718/
https://www.ncbi.nlm.nih.gov/pubmed/26858266
http://dx.doi.org/10.1083/jcb.201508026
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