Tissue Engineering of a Differentiated Cardiac Muscle Construct
Open accessAbstract
Cardiac tissue engineering is an emerging field. The suitability of engineered heart tissue (EHT) for both in vitro and in vivo applications will depend on the degree of syncytoid tissue formation and cardiac myocyte differentiation in vitro, contractile function, and electrophysiological properties. Here, we demonstrate that cardiac myocytes from neonatal rats, when mixed with collagen I and matrix factors, cast in circular molds, and subjected to phasic mechanical stretch, reconstitute ring-shaped EHTs that display important hallmarks of differentiated myocardium. Comparative histological analysis of EHTs with native heart tissue from newborn, 6-day-old, and adult rats revealed that cardiac cells in EHTs reconstitute intensively interconnected, longitudinally oriented, cardiac muscle bundles with morphological features resembling adult rather than immature native tissue. Confocal and electron microscopy demonstrated characteristic features of native differentiated myocardium; some of these features are absent in myocytes from newborn rats: (1) highly organized sarcomeres in registry; (2) adherens junctions, gap junctions, and desmosomes; (3) a well-developed T-tubular system and dyad formation with the sarcoplasmic reticulum; and (4) a basement membrane surrounding cardiac myocytes. Accordingly, EHTs displayed contractile characteristics of native myocardium with a high ratio of twitch (0.4 to 0.8 mN) to resting tension (0.1 to 0.3 mN) and a strong β-adrenergic inotropic response. Action potential recordings demonstrated stable resting membrane potentials of −66 to −78 mV, fast upstroke kinetics, and a prominent plateau phase. The data indicate that EHTs represent highly differentiated cardiac tissue constructs, making EHTs a promising material for in vitro studies of cardiac function and tissue replacement therapy.
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Early engineered heart tissues were simple strips or rings made by casting cardiomyocytes in ECM-based gel.
“Early engineered heart tissues consisted of geometrically simple structures (strips or rings) made by casting cardiomyocytes in an extracellular matrix-based gel1–3.”
From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [3]
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- Authors
- Zimmermann, W.-H., Schneiderbanger, K., Schubert, P., Didié, M., Münzel, F., Heubach, J. F., Kostin, S., Neuhuber, W. L., & Eschenhagen, T.
- Affiliations
- Max Planck Society (DE)
- From the Institute of Experimental and Clinical Pharmacology and Toxicology (W.-H.Z., K.S., P.S., M.D., F.M., T.E.) and the Institute of Anatomy (W.L.N.), Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany; the Institute of Pharmacology and Toxicology (J.F.H.), Dresden University of Technology, Dresden, Germany; and the Department of Experimental Cardiology (S.K.), Max-Planck-Institute, Bad Nauheim, Germany.
- Venue
- Circulation Research
- Published
- 2002-02-08
- Volume
- 90
- Issue
- 2
- Pages
- 223-230
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2018474760
- Cited by
- 917
- References
- 39
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 20 · 2023: 27 · 2022: 27 · 2021: 38 · 2020: 40 · 2019: 42 · 2018: 36 · 2017: 48 · 2016: 43 · 2015: 60 · 2014: 67 · 2013: 39 · 2012: 50
- FWCI
- 22.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion, cc-by)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Es 88/8-2)
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- cardiac tissue engineering, engineered heart tissue, cardiomyocyte differentiation, mechanical stretch, type I collagen, sarcomere organization, gap junctions, desmosomes, action potential, contractile function
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Calcium, Cardiotonic Agents, Cell Differentiation, Cells, Cultured, Electric Stimulation, Feasibility Studies, Immunohistochemistry, Isometric Contraction, Isoproterenol, Microscopy, Electron, Myocardial Contraction, Myocardium, Organoids, Sarcomeres, Tissue Engineering, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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