Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

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

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Article number4566
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Bioprinting
Induced Pluripotent Stem Cells
Biocompatible Materials
Cardiac Myocytes
Endothelial Cells
Fibroblasts
Action Potentials
Fluorescent Antibody Technique
Stem Cells
Immunohistochemistry
Video Microscopy
Connexin 43
Connexins
Treatment Failure
Blood Vessels
Cell Survival
Myocardium
Heart Failure
Staining and Labeling
Light

ASJC Scopus subject areas

  • General

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Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. / Ong, Chin Siang; Fukunishi, Takuma; Zhang, Huaitao; Huang, Chen Yu; Nashed, Andrew; Blazeski, Adriana; Disilvestre, Deborah; Vricella, Luca; Conte, John; Tung, Leslie; Tomaselli, Gordon F.; Hibino, Narutoshi.

In: Scientific Reports, Vol. 7, No. 1, 4566, 01.12.2017.

Research output: Contribution to journalArticle

Ong CS, Fukunishi T, Zhang H, Huang CY, Nashed A, Blazeski A et al. Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. Scientific Reports. 2017 Dec 1;7(1). 4566. Available from, DOI: 10.1038/s41598-017-05018-4
Ong, Chin Siang ; Fukunishi, Takuma ; Zhang, Huaitao ; Huang, Chen Yu ; Nashed, Andrew ; Blazeski, Adriana ; Disilvestre, Deborah ; Vricella, Luca ; Conte, John ; Tung, Leslie ; Tomaselli, Gordon F. ; Hibino, Narutoshi. / Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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