Fabrication of Pulsatile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces
Top Cited Papers
- 22 February 2002
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 90 (3), e40
- https://doi.org/10.1161/hh0302.105722
Abstract
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.Keywords
This publication has 33 references indexed in Scilit:
- Thermo-Responsive Culture Dishes Allow the Intact Harvest of Multilayered Keratinocyte Sheets without Dispase by Reducing TemperatureTissue Engineering, 2001
- Cardiomyocyte Grafting for Cardiac Repair: Graft Cell Death and Anti-Death StrategiesJournal of Molecular and Cellular Cardiology, 2001
- Two-Dimensional Manipulation of Cardiac Myocyte Sheets Utilizing Temperature-Responsive Culture Dishes Augments the Pulsatile AmplitudeTissue Engineering, 2001
- Growth hormone and the heartClinical Endocrinology, 2001
- Cardiac Organogenesisin Vitro: Reestablishment of Three-Dimensional Tissue Architecture by Dissociated Neonatal Rat Ventricular CellsTissue Engineering, 1999
- Cardiomyocytes can be generated from marrow stromal cells in vitroJCI Insight, 1999
- Skeletal myoblast transplantation for repair of myocardial necrosis.JCI Insight, 1996
- The Expression, Phosphorylation, and Localization of Connexin 43 and Gap-Junctional Intercellular Communication during the Establishment of a Synchronized Contraction of Cultured Neonatal Rat Cardiac MyocytesExperimental Cell Research, 1994
- A novel recovery system for cultured cells using plasma‐treated polystyrene dishes grafted with poly(N‐isopropylacrylamide)Journal of Biomedical Materials Research, 1993
- Tissue EngineeringScience, 1993