Abstract 11694: Genetic Modification of Ckit+ Cardiac Stem Cells to Overexpress Pim1 Enhances their Cardioreparative Ability After Intramyocardial Delivery
Background: Pim-1 kinase plays an important role in cell division, survival and commitment towards myocardial cell lineage. We tested the hypothesis that overexpression of Pim1 enhances the cardioreparative effect of ckit+ cardiac stem cells (CSCs).
Methods: Accordingly we treated immunosupressed Yorkshire pigs (n=27) with human ckit+ CSCs (n=6), Pim1 modified human ckit+ CSCs (n=9) or PBS (n=12) two weeks after the induction of MI. Cardiac MRI was obtained before and after cell administration.
Results: The Pim1 treated group had a ~5-fold decrease in scar mass at 8 weeks post transplantation compared to ckit+ CSCs (25.7%±3.7% vs. 5.5%±4.96%, p<0.05) (Fig.1A). In addition Pim1+ CSCs injections produced a greater reduction in scar mass as a % of left ventricular mass compared to ckit+ CSCs at 8 weeks (-56.4%±3.57% vs. -35.4%±7.89%, p<0.05) (Fig.1B). While both CSCs reduced scar size at 4 weeks post injection (p<0.001) compared to the control group, only the Pim1 group sustained that reduction at 8 weeks post injection (p<0.001) (Fig.1A). There were no adverse events associated with stem cell therapy.
Conclusions: The beneficial effect of intramyocardial delivery of CSCs to infarcted porcine hearts was significantly enhanced and persistent when they overexpress Pim1. This approach provides a rationale for further exploration of the genetic modification of stem cells and consequent translation to clinical trials. Figure 1. Reduction of scar tissue after human Cardiac Stem Cells intramyocardial delivery
- © 2012 by American Heart Association, Inc.