Ryo Noguchi1, Koichi Nakayama2, Manabu Itoh3, Keiji Kamohara3, Kojirou Furukawa3, Jun-ichi Oyama4, Koichi Node4, Shigeki Morita3. 1. Department of Thoracic and Cardiovascular Surgery. Electronic address: noguchi2@cc.saga-u.ac.jp. 2. Biomedical Engineering Course Advanced Technology, Fusion Graduate School of Science and Engineering. 3. Department of Thoracic and Cardiovascular Surgery. 4. Department of Cardiology, Saga University, Saga City, Japan.
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.
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: Martin L Tomov; Carmen J Gil; Alexander Cetnar; Andrea S Theus; Bryanna J Lima; Joy E Nish; Holly D Bauser-Heaton; Vahid Serpooshan Journal: Curr Cardiol Rep Date: 2019-08-01 Impact factor: 2.931
Authors: Tracy A Hookway; Oriane B Matthys; Federico N Mendoza-Camacho; Sarah Rains; Jessica E Sepulveda; David A Joy; Todd C McDevitt Journal: Tissue Eng Part A Date: 2019-05 Impact factor: 3.845