Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Abstract We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids. Cardiac patch...
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Nature Portfolio
2017
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oai:doaj.org-article:6e7b7ecb133a4b4abea17c9f5d020bd82021-12-02T15:06:14ZBiomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes10.1038/s41598-017-05018-42045-2322https://doaj.org/article/6e7b7ecb133a4b4abea17c9f5d020bd82017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05018-4https://doaj.org/toc/2045-2322Abstract We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids. Cardiac patches were created from spheroids (CM:FB:EC = 70:15:15, 70:0:30, 45:40:15) using a 3D bioprinter. Cardiac patches were analyzed with light and video microscopy, immunohistochemistry, immunofluorescence, cell viability assays and optical electrical mapping. Cardiac tissue patches of all cell ratios beat spontaneously after 3D bioprinting. Patches exhibited ventricular-like action potential waveforms and uniform electrical conduction throughout the patch. Conduction velocities were higher and action potential durations were significantly longer in patches containing a lower percentage of FBs. Immunohistochemistry revealed staining for CM, FB and EC markers, with rudimentary CD31+ blood vessel formation. Immunofluorescence revealed the presence of Cx43, the main cardiac gap junction protein, localized to cell-cell borders. In vivo implantation suggests vascularization of 3D bioprinted cardiac patches with engraftment into native rat myocardium. This constitutes a significant step towards a new generation of stem cell-based treatment for heart failure.Chin Siang OngTakuma FukunishiHuaitao ZhangChen Yu HuangAndrew NashedAdriana BlazeskiDeborah DiSilvestreLuca VricellaJohn ConteLeslie TungGordon F. TomaselliNarutoshi HibinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Chin Siang Ong Takuma Fukunishi Huaitao Zhang Chen Yu Huang Andrew Nashed Adriana Blazeski Deborah DiSilvestre Luca Vricella John Conte Leslie Tung Gordon F. Tomaselli Narutoshi Hibino Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes |
description |
Abstract We have developed a novel method to deliver stem cells using 3D bioprinted cardiac patches, free of biomaterials. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), fibroblasts (FB) and endothelial cells (EC) were aggregated to create mixed cell spheroids. Cardiac patches were created from spheroids (CM:FB:EC = 70:15:15, 70:0:30, 45:40:15) using a 3D bioprinter. Cardiac patches were analyzed with light and video microscopy, immunohistochemistry, immunofluorescence, cell viability assays and optical electrical mapping. Cardiac tissue patches of all cell ratios beat spontaneously after 3D bioprinting. Patches exhibited ventricular-like action potential waveforms and uniform electrical conduction throughout the patch. Conduction velocities were higher and action potential durations were significantly longer in patches containing a lower percentage of FBs. Immunohistochemistry revealed staining for CM, FB and EC markers, with rudimentary CD31+ blood vessel formation. Immunofluorescence revealed the presence of Cx43, the main cardiac gap junction protein, localized to cell-cell borders. In vivo implantation suggests vascularization of 3D bioprinted cardiac patches with engraftment into native rat myocardium. This constitutes a significant step towards a new generation of stem cell-based treatment for heart failure. |
format |
article |
author |
Chin Siang Ong Takuma Fukunishi Huaitao Zhang Chen Yu Huang Andrew Nashed Adriana Blazeski Deborah DiSilvestre Luca Vricella John Conte Leslie Tung Gordon F. Tomaselli Narutoshi Hibino |
author_facet |
Chin Siang Ong Takuma Fukunishi Huaitao Zhang Chen Yu Huang Andrew Nashed Adriana Blazeski Deborah DiSilvestre Luca Vricella John Conte Leslie Tung Gordon F. Tomaselli Narutoshi Hibino |
author_sort |
Chin Siang Ong |
title |
Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes |
title_short |
Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes |
title_full |
Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes |
title_fullStr |
Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes |
title_full_unstemmed |
Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes |
title_sort |
biomaterial-free three-dimensional bioprinting of cardiac tissue using human induced pluripotent stem cell derived cardiomyocytes |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/6e7b7ecb133a4b4abea17c9f5d020bd8 |
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