Aim: 

The electrophysiological effects of stem cell based therapy in heart repair are not established. We addressed this issue in a rat model of chronic myocardial infarction (MI). Regenerative treatment consisted of intra-myocardial injection of syngeneic cardiac stem cells (CSCs), either alone (MI-cells) or with IGF-1 + HGF (MI-cells+GF).

Methods: 

Eleven male adult Wistar rats with 4-week old MI were assigned to MI-cells treatment group and 12 to MI-cells+GF. To detect regenerative processes EGFP⁺ and Quantum Dots labeled cells were used. Animals were tested for proneness to stress-induced (resident-intruder test) ventricular arrhythmias (VAs), by telemetry ECG recordings prior and two weeks after treatment. ECGs were also analyzed for heart rate based indices of cardiac autonomic control (SD_RR and r-MSSD). Eventually, hemodynamics measurements were invasively performed. At sacrifice, the hearts were fixed through perfusion for morphometry and immuno-histochemical studies.

Results: 

The MI-cells+GF treatment reduced VAs by four-fold in 100% of the rats (p < 0.02), whereas MI-cells treatment was ineffective. Heart rate, SD_RR and r-MSSD had similar values in all rats. In both groups, cardiac mechanical competence was ameliorated and clusters of cycling small myocytes expressing Cx43 and neovascularisation were present in the infarcted area.

Conclusions: 

Treatment with MI-cells+GF resulted in newly formed electro-mechanical competent cardiac tissue as a consequence of (i) the natural role of CSCs in heart repair, and (ii) an increased engraftment and differentiation of CSCs through the added cytokines.