Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo
Enoch Yeung
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorTakuma Fukunishi
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorYang Bai
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Department of Cardiac Surgery, The First Hospital of Jilin University, Changchun, China
Search for more papers by this authorDjahida Bedja
Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorIsaree Pitaktong
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorGunnar Mattson
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorAnjana Jeyaram
Fischell Department of Bioengineering, University of Maryland, College Park, MD
Search for more papers by this authorCecillia Lui
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorChin Siang Ong
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorTakahiro Inoue
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorHiroshi Matsushita
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorSara Abdollahi
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorSteven M. Jay
Fischell Department of Bioengineering, University of Maryland, College Park, MD
Search for more papers by this authorCorresponding Author
Narutoshi Hibino
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Correspondence
Narutoshi Hibino, Division of Cardiac Surgery, The Johns Hopkins Hospital, Zayed 7107, 1800 Orleans St, Baltimore, MD 21287.
Email: [email protected]
Search for more papers by this authorEnoch Yeung
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorTakuma Fukunishi
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorYang Bai
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Department of Cardiac Surgery, The First Hospital of Jilin University, Changchun, China
Search for more papers by this authorDjahida Bedja
Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorIsaree Pitaktong
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorGunnar Mattson
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorAnjana Jeyaram
Fischell Department of Bioengineering, University of Maryland, College Park, MD
Search for more papers by this authorCecillia Lui
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorChin Siang Ong
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorTakahiro Inoue
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorHiroshi Matsushita
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorSara Abdollahi
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorSteven M. Jay
Fischell Department of Bioengineering, University of Maryland, College Park, MD
Search for more papers by this authorCorresponding Author
Narutoshi Hibino
Department of Surgery, Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, MD
Correspondence
Narutoshi Hibino, Division of Cardiac Surgery, The Johns Hopkins Hospital, Zayed 7107, 1800 Orleans St, Baltimore, MD 21287.
Email: [email protected]
Search for more papers by this authorAbstract
One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation.
CONFLICT OF INTEREST
The authors have that there is no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| TERM2954-supp-0001-sup_fs1.tiffTIFF image, 857.7 KB |
Figure S1. Masson Trichrome staining of the rat heart 4 weeks after surgery. Blue: the area of fibrosis, red: represents normal myocardium. Top Row. The control group. Bottom Row. The patch group |
| TERM2954-supp-0002-sup_fs2.tiffTIFF image, 857.7 KB |
Figure S2. Quantification of EV concentration, the EV secretion from the patch increased over 4 weeks after fabrication |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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