Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns
Abstract Cardiac two-dimensional tissues were engineered using biomimetic micropatterns based on the fibronectin-rich extracellular matrix (ECM) of the embryonic heart. The goal of this developmentally-inspired, in vitro approach was to identify cell–cell and cell-ECM interactions in the microenviro...
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2021
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oai:doaj.org-article:a417c199a2ca4f92a91dbbc8d97c7b132021-12-02T17:51:21ZEngineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns10.1038/s41598-021-87550-y2045-2322https://doaj.org/article/a417c199a2ca4f92a91dbbc8d97c7b132021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87550-yhttps://doaj.org/toc/2045-2322Abstract Cardiac two-dimensional tissues were engineered using biomimetic micropatterns based on the fibronectin-rich extracellular matrix (ECM) of the embryonic heart. The goal of this developmentally-inspired, in vitro approach was to identify cell–cell and cell-ECM interactions in the microenvironment of the early 4-chambered vertebrate heart that drive cardiomyocyte organization and alignment. To test this, biomimetic micropatterns based on confocal imaging of fibronectin in embryonic chick myocardium were created and compared to control micropatterns designed with 2 or 20 µm wide fibronectin lines. Results show that embryonic chick cardiomyocytes have a unique density-dependent alignment on the biomimetic micropattern that is mediated in part by N-cadherin, suggesting that both cell–cell and cell-ECM interactions play an important role in the formation of aligned myocardium. Human induced pluripotent stem cell-derived cardiomyocytes also showed density-dependent alignment on the biomimetic micropattern but were overall less well organized. Interestingly, the addition of human adult cardiac fibroblasts and conditioning with T3 hormone were both shown to increase human cardiomyocyte alignment. In total, these results show that cardiomyocyte maturation state, cardiomyocyte-cardiomyocyte and cardiomyocyte-fibroblast interactions, and cardiomyocyte-ECM interactions can all play a role when engineering anisotropic cardiac tissues in vitro and provides insight as to how these factors may influence cardiogenesis in vivo.Ivan BatalovQuentin JalleratSean KimJacqueline BlileyAdam W. FeinbergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Ivan Batalov Quentin Jallerat Sean Kim Jacqueline Bliley Adam W. Feinberg Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
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Abstract Cardiac two-dimensional tissues were engineered using biomimetic micropatterns based on the fibronectin-rich extracellular matrix (ECM) of the embryonic heart. The goal of this developmentally-inspired, in vitro approach was to identify cell–cell and cell-ECM interactions in the microenvironment of the early 4-chambered vertebrate heart that drive cardiomyocyte organization and alignment. To test this, biomimetic micropatterns based on confocal imaging of fibronectin in embryonic chick myocardium were created and compared to control micropatterns designed with 2 or 20 µm wide fibronectin lines. Results show that embryonic chick cardiomyocytes have a unique density-dependent alignment on the biomimetic micropattern that is mediated in part by N-cadherin, suggesting that both cell–cell and cell-ECM interactions play an important role in the formation of aligned myocardium. Human induced pluripotent stem cell-derived cardiomyocytes also showed density-dependent alignment on the biomimetic micropattern but were overall less well organized. Interestingly, the addition of human adult cardiac fibroblasts and conditioning with T3 hormone were both shown to increase human cardiomyocyte alignment. In total, these results show that cardiomyocyte maturation state, cardiomyocyte-cardiomyocyte and cardiomyocyte-fibroblast interactions, and cardiomyocyte-ECM interactions can all play a role when engineering anisotropic cardiac tissues in vitro and provides insight as to how these factors may influence cardiogenesis in vivo. |
format |
article |
author |
Ivan Batalov Quentin Jallerat Sean Kim Jacqueline Bliley Adam W. Feinberg |
author_facet |
Ivan Batalov Quentin Jallerat Sean Kim Jacqueline Bliley Adam W. Feinberg |
author_sort |
Ivan Batalov |
title |
Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
title_short |
Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
title_full |
Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
title_fullStr |
Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
title_full_unstemmed |
Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
title_sort |
engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/a417c199a2ca4f92a91dbbc8d97c7b13 |
work_keys_str_mv |
AT ivanbatalov engineeringalignedhumancardiacmuscleusingdevelopmentallyinspiredfibronectinmicropatterns AT quentinjallerat engineeringalignedhumancardiacmuscleusingdevelopmentallyinspiredfibronectinmicropatterns AT seankim engineeringalignedhumancardiacmuscleusingdevelopmentallyinspiredfibronectinmicropatterns AT jacquelinebliley engineeringalignedhumancardiacmuscleusingdevelopmentallyinspiredfibronectinmicropatterns AT adamwfeinberg engineeringalignedhumancardiacmuscleusingdevelopmentallyinspiredfibronectinmicropatterns |
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