Pulsatile tubular cardiac tissues fabricated by wrapping human iPS cells-derived cardiomyocyte sheets

Abstract

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.

Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function

“…This represents an improvement in the dynamic range of 2 orders of magnitude and is based on the use of a microfluidic device as the machinery to detect and quantify the force. A recent study reported a measurement system for the pressure produced by the cell sheet contractile force utilizing a tube structure prepared by cell sheets 41 . The detection limit of the tube-based method is approximately 4 Pa, which is larger than that of the present method, which is 1.1 Pa and corresponds to the displacement of a particle by 1.6 μm in a microchannel.…”

Fundamental Technologies and Recent Advances of Cell-Sheet-Based Tissue Engineering

“…Electrical stimulation has also been utilized for the maturation of muscle cell sheets [ 62 , 63 , 64 ]. In cell sheets, cells not only physically but also electrically connect with each other through gap junctions.…”

“…For myocardial cell sheets, our group reported that electrical stimulation improved the function of the cell sheets. The spontaneous beating of each cell became synchronized due to the formation of an electrical connection within a cell sheet [ 63 ]. Further, the function of each cell can also be enhanced by improving the beating rate.…”

Review on Mechanical Support and Cell-Based Therapies for the Prevention and Recovery of the Failed Fontan-Kreutzer Circulation

“…Pacing and engraftment failure were also apparent in a small portion of rats at each time point ( 90 ). This group is now developing a new method to combine hiPSC derived cardiomyocytes with human dermal fibroblasts to increase maturation of cardiomyocytes, and thus better recapitulate native myocardium function, in vitro ( 92 ).…”