Abstract 18046: Pim1 Kinase Overexpression Enhances ckit+ Cardiac Stem Cells Cardioreparative Ability After Intramyocardial Delivery in a Swine Model
Introduction: Pim-1 kinase plays an important role in cell division, survival and commitment of precursor cells towards a myocardial lineage.
Hypothesis: We hypothesized that overexpression of Pim1 in ckit+ cardiac stem cell (CSCs) enhances their cardioreparative effect
Methods: We treated immunosuppressed Yorkshire swine (n=29) with human ckit+ CSCs (n=10), Pim1 modified human ckit+ CSCs (n=9) or PBS (n=10) two weeks after MI. Cardiac MRI and PV loops were obtained before and after cell administration.
Results: Whereas both pim1- and pim1+ c-kit cells reduced MI size, the Pim1 group had a ~3-fold decrease in scar mass at 8 weeks post transplantation compared to ckit+ (–29.2±2.7% vs. –8.4±0.7%, p<0.003). Pim1+ CSC injections also produced a 2-fold increase of viable mass compared to ckit+ CSCs at 8 weeks (113.7±7.2% vs 65.6±6.8%, p<0.003; Fig. 1B), a greater increase in regional contractility (Ecc) at infarct (–10±1.1 vs. –6.1±0.3, p<0.05, Fig. 1D) and border zones (–12.3±1 vs. –8.4±0.5, p<0.05; Fig. 1E). Both CSC types increased ejection fraction at 4 weeks that was only sustained in the pim1 group at 8 weeks compared to placebo (change from pre-injection pim1: 12.7±1.7 vs. ckit: 5.1±3.1 vs placebo -0.7±2.5%, two way ANOVA p<0.001). Afterload was similarly reduced (Arterial Elastance; –27.8±6.5% vs. -22.2±5.3%, two way ANOVA p=0.5) compared to pre-injection which resulted in mechanoenergetic recoupling that was greater in the Pim1 group (Cardiac Efficiency; 0.46±0.03 vs 0.32±0.01; p=0.005).
Conclusions: The effect of intramyocardial delivery of CSCs to infarcted porcine hearts was enhanced by the overexpression of Pim1. This approach provides a rationale for further exploration of the genetic modification of stem cells and consequent translation to clinical trials.
Author Disclosures: V. Karantalis: Other Research Support; Significant; AHA post doctoral fellowship. V.Y. Suncion: None. F. McCall: None. B. Wang: None. L. Bagno: None. S. Golpanian: None. A. Wolf: None. A. Williams: None. J. Rodriguez: None. D. Valdes: None. M. Rosado: None. S. Mohsin: None. M. Sussman: None. J. Da Silva: None. A. Morales: None. J.M. Hare: Employment; Modest; Vestion. Ownership Interest; Modest; Biscayne. Ownership Interest; Significant; Vestion Inc.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.