Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
Circulation Research. 2002
Published online before print January 24, 2002, doi: 10.1161/hh0302.105722
A more recent version of this article appeared on February 22, 2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
90/3/e40    most recent
hh0302.105722v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shimizu, T.
Right arrow Articles by Okano, T.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Shimizu, T.
Right arrow Articles by Okano, T.
Related Collections
Right arrow Other Treatment
Right arrow CV surgery: other

Submitted on October 15, 2001
Revised on January 14, 2002
Accepted on January 14, 2002

Fabrication of Pulsatile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces

Tatsuya Shimizu ; Masayuki Yamato ; Yuki Isoi ; Takumitsu Akutsu ; Takeshi Setomaru ; Kazuhiko Abe ; Akihiko Kikuchi ; Mitsuo Umezu ; and Teruo Okano *

From the Institute of Advanced Biomedical Engineering and Science (T.S., M.Y., Y.I., K.A., A.K., T.O.), Tokyo Women's Medical University; and the Department of Mechanical Engineering (T.A., T.S., M.U.), Waseda University, Shinjuku-ku, Tokyo, Japan.

* To whom correspondence should be addressed. E-mail: tokano{at}lab.twmu.ac.jp.

Recent progress in cell transplantation therapy to repair impaired hearts has encouraged further attempts to bioengineer 3-dimensional (3-D) heart tissue from cultured cardiomyocytes. Cardiac tissue engineering is currently pursued utilizing conventional technology to fabricate 3-D biodegradable scaffolds as a temporary extracellular matrix. By contrast, new methods are now described to fabricate pulsatile cardiac grafts using new technology that layers cell sheets 3-dimensionally. We apply novel cell culture surfaces grafted with temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), from which confluent cells detach as a cell sheet simply by reducing temperature without any enzymatic treatments. Neonatal rat cardiomyocyte sheets detached from PIPAAm-grafted surfaces were overlaid to construct cardiac grafts. Layered cell sheets began to pulse simultaneously and morphological communication via connexin43 was established between the sheets. When 4 sheets were layered, engineered constructs were macroscopically observed to pulse spontaneously. In vivo, layered cardiomyocyte sheets were transplanted into subcutaneous tissues of nude rats. Three weeks after transplantation, surface electrograms originating from transplanted grafts were detected and spontaneous beating was macroscopically observed. Histological studies showed characteristic structures of heart tissue and multiple neovascularization within contractile tissues. Constructs transplanted into 3-week-old rats exhibited more cardiomyocyte hypertrophy and less connective tissue than those placed into 8-week-old rats. Long-term survival of pulsatile cardiac grafts was confirmed up to 12 weeks. These results demonstrate that electrically communicative pulsatile 3-D cardiac constructs were achieved both in vitro and in vivo by layering cardiomyocyte sheets. Cardiac tissue engineering based on this technology may prove useful for heart model fabrication and cardiovascular tissue repair. The full text of this article is available at http://www.circresaha.org.


Key words: cardiac tissue engineering • temperature-responsive cell culture surface • cell sheet • electrical communication • angiogenesis




This article has been cited by other articles:


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
K. Hobo, T. Shimizu, H. Sekine, T. Shin'oka, T. Okano, and H. Kurosawa
Therapeutic Angiogenesis Using Tissue Engineered Human Smooth Muscle Cell Sheets
Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 637 - 643.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. N. Morritt, S. K. Bortolotto, R. J. Dilley, X. Han, A. R. Kompa, D. McCombe, C. E. Wright, S. Itescu, J. A. Angus, and W. A. Morrison
Cardiac Tissue Engineering in an In Vivo Vascularized Chamber
Circulation, January 23, 2007; 115(3): 353 - 360.
[Abstract] [Full Text] [PDF]


Home page
Eur. J. Cardiothorac. Surg.Home page
K. H. Wu, Y. L. Liu, B. Zhou, and Z. C. Han
Cellular therapy and myocardial tissue engineering: the role of adult stem and progenitor cells
Eur. J. Cardiothorac. Surg., November 1, 2006; 30(5): 770 - 781.
[Abstract] [Full Text] [PDF]


Home page
Arch OphthalmolHome page
J.-Y. Lai, K.-H. Chen, W.-M. Hsu, G.-H. Hsiue, and Y.-H. Lee
Bioengineered Human Corneal Endothelium for Transplantation
Arch Ophthalmol, October 1, 2006; 124(10): 1441 - 1448.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
K. L. Christman and R. J. Lee
Biomaterials for the Treatment of Myocardial Infarction
J. Am. Coll. Cardiol., September 5, 2006; 48(5): 907 - 913.
[Abstract] [Full Text] [PDF]


Home page
Biophys. JHome page
C. F. Asnes, J. P. Marquez, E. L. Elson, and T. Wakatsuki
Reconstitution of the Frank-Starling Mechanism in Engineered Heart Tissues
Biophys. J., September 1, 2006; 91(5): 1800 - 1810.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
W.-H. Zimmermann, M. Didie, S. Doker, I. Melnychenko, H. Naito, C. Rogge, M. Tiburcy, and T. Eschenhagen
Heart muscle engineering: An update on cardiac muscle replacement therapy
Cardiovasc Res, August 1, 2006; 71(3): 419 - 429.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
H. Naito, I. Melnychenko, M. Didie, K. Schneiderbanger, P. Schubert, S. Rosenkranz, T. Eschenhagen, and W.-H. Zimmermann
Optimizing Engineered Heart Tissue for Therapeutic Applications as Surrogate Heart Muscle
Circulation, July 4, 2006; 114(1_suppl): I-72 - I-78.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
H. Sekine, T. Shimizu, J. Yang, E. Kobayashi, and T. Okano
Pulsatile Myocardial Tubes Fabricated With Cell Sheet Engineering
Circulation, July 4, 2006; 114(1_suppl): I-87 - I-93.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
X.-M. Guo, Y.-S. Zhao, H.-X. Chang, C.-Y. Wang, L.-L. E, X.-A. Zhang, C.-M. Duan, L.-Z. Dong, H. Jiang, J. Li, et al.
Creation of Engineered Cardiac Tissue In Vitro From Mouse Embryonic Stem Cells
Circulation, May 9, 2006; 113(18): 2229 - 2237.
[Abstract] [Full Text] [PDF]


Home page
IOVSHome page
Y. Hayashida, K. Nishida, M. Yamato, J. Yang, H. Sugiyama, K. Watanabe, Y. Hori, N. Maeda, A. Kikuchi, T. Okano, et al.
Transplantation of Tissue-Engineered Epithelial Cell Sheets after Excimer Laser Photoablation Reduces Postoperative Corneal Haze
Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 552 - 557.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
H. Kondoh, Y. Sawa, S. Miyagawa, S. Sakakida-Kitagawa, I. A. Memon, N. Kawaguchi, N. Matsuura, T. Shimizu, T. Okano, and H. Matsuda
Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters
Cardiovasc Res, February 1, 2006; 69(2): 466 - 475.
[Abstract] [Full Text] [PDF]


Home page
J. Thorac. Cardiovasc. Surg.Home page
I. A. Memon, Y. Sawa, N. Fukushima, G. Matsumiya, S. Miyagawa, S. Taketani, S. K. Sakakida, H. Kondoh, A. N. Aleshin, T. Shimizu, et al.
Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets
J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1333 - 1341.
[Abstract] [Full Text] [PDF]


Home page
J. Thorac. Cardiovasc. Surg.Home page
O. Ishii, M. Shin, T. Sueda, and J. P. Vacanti
In vitro tissue engineering of a cardiac graft using a degradable scaffold with an extracellular matrix-like topography
J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1358 - 1363.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
Y. Itabashi, S. Miyoshi, S. Yuasa, J. Fujita, T. Shimizu, T. Okano, K. Fukuda, and S. Ogawa
Analysis of the electrophysiological properties and arrhythmias in directly contacted skeletal and cardiac muscle cell sheets
Cardiovasc Res, August 15, 2005; 67(3): 561 - 570.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
D. A. Narmoneva, R. Vukmirovic, M. E. Davis, R. D. Kamm, and R. T. Lee
Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization: Implications for Cardiac Regeneration
Circulation, August 24, 2004; 110(8): 962 - 968.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
B. C. Heng, H. K. Haider, E. K.-W. Sim, T. Cao, and S. C. Ng
Strategies for directing the differentiation of stem cells into the cardiomyogenic lineage in vitro
Cardiovasc Res, April 1, 2004; 62(1): 34 - 42.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M. Radisic, L. Yang, J. Boublik, R. J. Cohen, R. Langer, L. E. Freed, and G. Vunjak-Novakovic
Medium perfusion enables engineering of compact and contractile cardiac tissue
Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H507 - H516.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
H. J. Evans, J. K. Sweet, R. L. Price, M. Yost, and R. L. Goodwin
Novel 3D culture system for study of cardiac myocyte development
Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H570 - H578.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
J. D. Dowell, M. Rubart, K. B.S. Pasumarthi, M. H. Soonpaa, and L. J. Field
Myocyte and myogenic stem cell transplantation in the heart
Cardiovasc Res, May 1, 2003; 58(2): 336 - 350.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
H. Masuda and T. Asahara
Post-natal endothelial progenitor cells for neovascularization in tissue regeneration
Cardiovasc Res, May 1, 2003; 58(2): 390 - 398.
[Abstract] [Full Text] [PDF]