Background

Somatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M) SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction.

Methods

Myocardial injury was induced by ameroid ring placement in immunosuppressed female mini pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n= 7), SMs (n= 7), and MSCs (n= 7). Control pigs underwent sham operation (n= 8).

Results

Cell therapy improved functional recovery 2 months after myocardial infarction, as evidenced by increased ejection fraction (iPS-CM,+ 7.3%±2.2% and SM,+ 5.8%±5.4% vs control,− 4.4%±3.8%; P< 0.05). The analysis of regional contractile function in the infarcted zone revealed an increase in transverse peak strain (iPS-CM,+ 4.6%±2.2% vs control,− 3.8%±4.7%; P< 0.05). The C-11 acetate kinetic analysis by positron emission tomography showed that the work-metabolic cardiac energy efficacy increased by the transplantation of iPS-CMs, but was reduced by the other cell types. This was accompanied by decreased myocardial wall stress in the infarcted zone (iPS-CM,− 27.6±32.3 Pa and SM,− 12.8±27 Pa vs control,+ 40.5±33.9 Pa; P< 0.05).

Conclusions

The iPS-CM is superior to other somatic cell sources in terms of improving regional contractile function and cardiac bioenergetic efficiency, suggesting greater clinical benefits in severely damaged myocardium.