Scaffold-Free Human Cardiac Tissue Patch Created from Embryonic Stem Cells

Progress in cardiac tissue engineering has been limited by (1) unfavorable cell and host responses to biomaterial scaffolds, (2) lack of suitable human cardiomyocyte sources, and (3) lack of fabrication techniques for scalable production of engineered tissue constructs. Here we report a novel and sc...

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Bibliographic Details
Published in:Tissue engineering. Part A 2009-06, Vol.15 (6), p.1211-1222
Main Authors: Stevens, Kelly R., Pabon, Lil, Muskheli, Veronica, Murry, Charles E.
Format: Article
Language:English
Subjects:
Biomedical materials
Calcium Signaling
Cell Differentiation
Cell Proliferation
Cell Size
Cells, Cultured
Cellular biology
Embryonic stem cells
Embryonic Stem Cells - cytology
Heart
Heart muscle
Humans
Intracellular Space - metabolism
Myocardium - cytology
Myocytes, Cardiac - cytology
Physiological aspects
Stem cells
Time Factors
Tissue engineering
Tissue Engineering - methods
Tissue Scaffolds
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Summary:Progress in cardiac tissue engineering has been limited by (1) unfavorable cell and host responses to biomaterial scaffolds, (2) lack of suitable human cardiomyocyte sources, and (3) lack of fabrication techniques for scalable production of engineered tissue constructs. Here we report a novel and scalable method to generate scaffold-free human cardiac tissue patches. Human embryonic stem cells were differentiated to cardiomyocytes using activin A and BMP4 and placed into suspension on a rotating orbital shaker. Cells aggregated to form macroscopic disc-shaped patches of beating tissue after 2 days. Patch diameter was directly proportional to input cell number (approximately 11 mm with 12 million cells), and patches were 300–600 μm thick. Cardiomyocytes were concentrated around the patch edges and exhibited increased purity and maturation with time, comprising approximately 80% of total cells after 11 days. Noncardiac cell elements, primarily epithelium, were present at day 2 but were diminished markedly at later time points. Cardiomyocyte proliferation occurred throughout the patches at day 2 but declined by day 8. Patches exhibited automaticity and synchronous calcium transients, indicating electromechanical coupling. These novel scaffold-free human myocardial patches address critical challenges related to human cell sourcing and tissue fabrication that previously inhibited progress in cardiac tissue engineering.
ISSN:1937-3341
1937-335X
DOI:10.1089/ten.tea.2008.0151