Functional Cardiac Tissue Engineering

Abstract

Heart attack remains the leading cause of death in both men and women worldwide. Stem cell-based therapies, including the use of engineered cardiac tissues, have the potential to treat the massive cell loss and pathological remodeling resulting from heart attack. Specifically, embryonic and induced pluripotent stem cells are a promising source for generation of therapeutically relevant numbers of functional cardiomyocytes and engineering of cardiac tissues in vitro. This review will describe methodologies for successful differentiation of pluripotent stem cells towards the cardiovascular cell lineages as they pertain to the field of cardiac tissue engineering. The emphasis will be placed on comparing the functional maturation in engineered cardiac tissues and developing heart and on methods to quantify cardiac electrical and mechanical function at different spatial scales.

Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues

“…Conduction velocity is developmentally regulated. It is dependent upon gap junctional coupling, I Na —which depends on Na + conductance and the resting membrane potential—and cell size, properties that change during cardiac development [161]. …”

“…The spontaneous beat rate of hPSC-CMs has been reported to range from 21 to 84 beats per minute [73, 153, 175–178]. This spontaneous activity is present in CMs during early embryonic stage but is supplanted by a quiescent cell phenotype as development progresses [161]. …”

Biomaterial based cardiac tissue engineering and its applications

“…Biphasic pulses may be better for inducing action potential excitation because the two pulses act synergistically leading up to excitation [122]. The stimulus frequency can also control contractile behaviour and amplitudes, where increased frequency decreases contractile amplitude until a chaotic behaviour is reached at frequencies above the maximum capture rate [123]. However, the controlled ramp-up in stimulation frequency (1 to 3Hz and 1 to 6Hz) over a period of one week, has demonstrated beneficial effects on tissue maturation[115].…”

Multiscale technologies for treatment of ischemic cardiomyopathy

“…Incorporating gold nanowires in 3D biopolymeric (alginate) scaffolds has been recently demonstrated to bridge the non-conducting pore walls, allowing nanocomposite cardiac matrices to be engineered with remarkably improved electrical communication, cellular alignment, tissue integration and synchronous contractile function 102 . These cellular nano-constructs could be further used as cardiac patches in vivo to treat ischemic heart injuries at much lower risk of patch-induced cardiac arrhythmias 115,116 .…”