Journal
REGENERATIVE THERAPY
Volume 11, Issue -, Pages 297-305Publisher
ELSEVIER
DOI: 10.1016/j.reth.2019.09.001
Keywords
Human induced pluripotent stem cell; Cardiomyocyte; Three-dimensional tissue model; Tissue engineering; Regenerative medicine; Cell sheet
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Funding
- Creation of innovation centers for advanced interdisciplinary research areas Program in the Project for Developing Innovation Systems Cell Sheet Tissue Engineering Center (CSTEC) from the Ministry of Education, Culture, Sports, Science and Technology (ME
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The purpose of this study was to fabricate pulsatile tubular cardiac tissue using cell sheet based-tissue engineering. First, we fabricated human induced pluripotent stem cell (hiPSc)-derived cardiomyocyte sheets and normal human dermal fibroblast (NHDF) sheets which are harvested from temperature responsive culture dishes only by lowering the temperature. Then tubular cardiac tissues are formed by wrapping one hiPSc-derived cardiomyocyte sheet and three NHDF sheets around an octagonal column, and both ends of the tubular tissue were covered with fibrin and collagen gel. The octagonal column with the tubular tissue was connected to an in vitro circulation system in a culture box. After four-day culture, the cardiac tissue survived and pulsated spontaneously in the circulation system. Furthermore, the analysis with a Millar catheter inserted into the cardiac tubes revealed significant inner pressure changes generated by their beating. In addition, the tubular cardiac tissue pulsated in response to the electrical stimulation. Although histological analyses demonstrated that cardiac troponin T-positive cells stratified the inner surface of the tubular tissues, gene expression analyses showed an immature state of these cardiomyocytes. Thus, cell sheet-based tissue engineering realized human pulsatile tubular cardiac tissue fabrication and we believe that these tubular cardiac tissues should contribute to future drug screening and regenerative therapy for heart diseases. (C) 2019, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.
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