Table 4.

Comparison between PSC-based Cardiac Cell Therapy and in situ Heart Regeneration

Issues	PSC-based Cardiac Cell Therapy	in situ Heart Regeneration
Therapeutic mechanisms	Replacing the damaged myocardium through transplantation of in vitro generated cardiac cells into the heart	Modulating the heart’s own regenerative response by simulating or reprogramming endogenous cells
Cell sources	Theoretically unlimited amounts. Well-controlled cell type and quality.	Cell type, quality and amounts typically restricted and context-dependent.
In vitro bioengineering	Applicable	Not applicable
Cellular maturation	Fetal or neonatal cardiomyocytes-like features	Often adult cardiomyocyte-like features
Risk of tumor formation	Possible due to residue pluripotent cells	Possible due to modifying host genome by transgenes and uncontrollable transgene expression
Risk of immune rejection	Possible but ameliorable with iPS technology	Unlikely
Risk of arrhythmias	Possible due to autorhythmicity, immaturity and inorganization of graft cells	Possible due to potentially unpredictable and incomplete reprogramming
Graft survival and host-graft integration	Challenging	Not necessary
Ease of implementation	Low	Relatively high
Cost	Relatively high	Relatively low