title: Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease.
abstract: BACKGROUND
  The aim of our study was to develop a completely scaffold-free, viable, contractile cardiac tissue capable of being grafted into the damaged native heart.
  
  
  METHODS
  Our technology is based on the fundamental characteristics of the self-assembling nature of cells. We created contractile cardiac spheroids by plating a mixture of rat neonatal ventricular cardiomyocytes, human dermal fibroblasts, and human coronary microartery endothelial cells in ultralow attachment plates. First, the optimal cell ratios for the 3 cell sources were determined. Next, approximately 1 × 10(4) optimal spheroids were fused into a patch-like construct, and the morphologic characteristics and mechanical functions of these patches were evaluated. Finally, the cardiac patches were grafted into the hearts of F344 nude rats, and histologic studies were performed after transplantation.
  
  
  RESULTS
  Synchronous beating of the cardiac patch was confirmed electrophysiologically and mechanically. A micronetwork of endothelial cells was also demonstrated in the construct, and the histologic study performed 5 days after transplantation showed the grafts to be viable, with functioning microvascular structures inside the graft tissue.
  
  
  CONCLUSIONS
  We consider the application of our scaffold-free 3-dimensional tissue engineering technology to cardiac regeneration therapy is feasible and expect that this technology will become a promising tool for the treatment of end-stage heart failure.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery. Electronic address: noguchi2@cc.saga-u.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Noguchi
authors.affiliation: Biomedical Engineering Course Advanced Technology, Fusion Graduate School of Science and Engineering.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Thoracic and Cardiovascular Surgery.
authors.forename: Manabu
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Department of Thoracic and Cardiovascular Surgery.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kamohara
authors.affiliation: Department of Thoracic and Cardiovascular Surgery.
authors.forename: Kojirou
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Cardiology, Saga University, Saga City, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Oyama
authors.affiliation: Department of Cardiology, Saga University, Saga City, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
authors.affiliation: Department of Thoracic and Cardiovascular Surgery.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Morita
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000166:cytology; D006331:Heart Diseases / Q000601:surgery*; D016027:Heart Transplantation / Q000379:methods*; D021621:Imaging, Three-Dimensional; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
keywords: contractile cardiac tissue; dermal fibroblasts; heart disease; spheroids; ventricular cardiomyocytes