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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05018-4 |
| _version_ | 1818343933078405120 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T16:38:27Z |
| format | Article |
| id | doaj.art-6e7b7ecb133a4b4abea17c9f5d020bd8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T16:38:27Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6e7b7ecb133a4b4abea17c9f5d020bd82022-12-21T23:38:20ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-05018-4Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived CardiomyocytesChin Siang Ong0Takuma Fukunishi1Huaitao Zhang2Chen Yu Huang3Andrew Nashed4Adriana Blazeski5Deborah DiSilvestre6Luca Vricella7John Conte8Leslie Tung9Gordon F. Tomaselli10Narutoshi Hibino11Division of Cardiac Surgery, Johns Hopkins HospitalDivision of Cardiac Surgery, Johns Hopkins HospitalDivision of Cardiac Surgery, Johns Hopkins HospitalDivision of Cardiology, Johns Hopkins HospitalDivision of Cardiology, Johns Hopkins HospitalDepartment of Biomedical Engineering, Johns Hopkins UniversityDivision of Cardiology, Johns Hopkins HospitalDivision of Cardiac Surgery, Johns Hopkins HospitalDivision of Cardiac Surgery, Johns Hopkins HospitalDepartment of Biomedical Engineering, Johns Hopkins UniversityDivision of Cardiology, Johns Hopkins HospitalDivision of Cardiac Surgery, Johns Hopkins HospitalAbstract 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.https://doi.org/10.1038/s41598-017-05018-4 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-05018-4 |
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