Figure 4:

Electrical stimulation of cell culture leads to greater contractility in engineered cardiac tissue. Beating macrotissues were generated by seeding induced pluripotent stem cell-derived cardiomyocytes and human fibroblasts in a 3-dimensional porous scaffold and culturing for 14 days as either control (no electrical stimulation) or ‘CardioSlice’ (electrical stimulation applied whilst culturing). (A) Human cardiac macrotissues after 7 or 14 days of culture, either without (control) or with (CardioSlice) electrical stimulation (scale bars 2.5 mm) (see also Videos 1 and 2). (B) Contraction amplitude of control versus CardioSlice bioengineered cardiac tissues. Fractional contraction area (compared to area of the tissue at rest) is represented over time, and control tissue remains close to 1.0 when contracting whereas CardioSlice patches contract to 0.85 (85% of size of tissue at rest). (C) The percentage of FAC for control (unstimulated) versus electrically stimulated CardioSlice cardiac macrotissues. (D) MCR for control compared to electrically stimulated CardioSlice macrotissues when paced. At 14 days, CardioSlice macrotissues were able to be paced at over 4 Hz, approximately double the MCR of control tissues. (E) Beating cardiac macrotissue velocity maps after 14 days of culture. Blue colours and shorter white mini arrows represent lower velocities. Higher velocities (redder areas and longer mini arrows) were observed in CardioSlice macrotissues versus controls (scale bar 2.5 mm). (F) Alignment analysis comparing direction of the electrical field vector and subsequent beating direction of bioengineered cardiac tissues. The order parameter cos2θ was used: random distribution gives values close to 0 whereas parallel alignment gives values close to 1 (modified with permission from Valls-Margarit et al. [21]). FAC: fractional area change; MCR: maximum capture rate.