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Tissue Engineering of Vascularized Cardiac Muscle From Human Embryonic Stem Cells
Abstract
Transplantation of a tissue-engineered heart muscle represents a novel experimental therapeutic paradigm for myocardial diseases. However, this strategy has been hampered by the lack of sources for human cardiomyocytes and by the scarce vasculature in the ischemic area limiting the engraftment and survival of the transplanted muscle. Beyond the necessity of endothelial capillaries for the delivery of oxygen and nutrients to the grafted muscle tissue, interactions between endothelial and cardiomyocyte cells may also play a key role in promoting cell survival and proliferation. In the present study, we describe the formation of synchronously contracting engineered human cardiac tissue derived from human embryonic stem cells containing endothelial vessel networks. The 3D muscle consisted of cardiomyocytes, endothelial cells (ECs), and embryonic fibroblasts (EmFs). The formed vessels were further stabilized by the presence of mural cells originating from the EmFs. The presence of EmFs decreased EC death and increased EC proliferation. Moreover, the presence of endothelial capillaries augmented cardiomyocyte proliferation and did not hamper cardiomyocyte orientation and alignment. Immunostaining, ultrastructural analysis (using transmission electron microscopy), RT-PCR, pharmacological, and confocal laser calcium imaging studies demonstrated the presence of cardiac-specific molecular, ultrastructural, and functional properties of the generated tissue constructs with synchronous activity mediated by action potential propagation through gap junctions. In summary, this is the first report of the construction of 3D vascularized human cardiac tissue that may have unique applications for studies of cardiac development, function, and tissue replacement therapy.
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Prior studies have arranged hPSC-derived ventricular cardiomyocytes as monolayers and patches for electrophysiology and for surgical implantation.
“Although hPSC-vCMs have been organized as monolayers and patches for electrophysiological assessment [6–8] and even surgical engraftment [9–11]”
From Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells (2018) · cites this paper as [10]
The Generation of the Engineered Human Cardiac Tissue section describes hESC-derived cardiomyocytes seeded on three-dimensional scaffolds, and Impulse Propagation reports electrical activity in those constructs. The paper does not report surgical implantation or engraftment; it presents tissue replacement as a potential application. It also does not describe its constructs as monolayers. (LLM, conf=0.86)
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Metadata
- Authors
- Caspi, O., Lesman, A., Basevitch, Y., Gepstein, A., Arbel, G., Habib, I. H. M., Gepstein, L., & Levenberg, S.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- From the Sohnis Family Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine and the Rappaport Family Institute for Research in the Medical Sciences (O.C., A.G., G.A., I.H., M.H., L.G.), The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology; Department of Biomedical Engineering (A.L., Y.B., S.L.) and Biotechnology Interdisciplinary Unit (Y.B.), Technion-Israel Institute of Technology; and Cardiology Department (L.G.), Rambam Medical Center, Haifa,...
- Venue
- Circulation Research
- Published
- 2007-02-02
- Volume
- 100
- Issue
- 2
- Pages
- 263-272
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2153099809
- Cited by
- 558
- References
- 36
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 14 · 2021: 28 · 2020: 9 · 2019: 22 · 2018: 23 · 2017: 39 · 2016: 32 · 2015: 25 · 2014: 51 · 2013: 46 · 2012: 43
- FWCI
- 44.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- human embryonic stem cells, endothelial cells, cardiomyocytes, embryonic fibroblasts, mural cells, endothelial cell proliferation, cardiomyocyte proliferation, gap junctions, action potential propagation, myocardial ischemia
- MeSH terms
- Cells, Cultured, Coronary Vessels, Humans, Myocardium, Microscopy, Confocal, Neovascularization, Physiologic, Cell Culture Techniques, Tissue Engineering, Myocytes, Cardiac, Cell Proliferation, Embryonic Stem Cells
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