Abstract 2665: Cellular Cardiomyoplasty: Optimizing Cellular Dosage and Retention by Microencapsulation
Objective: There is no consensus regarding the optimal dose of marrow stromal cells (MSCs) for cellular cardiomyoplasty via direct intramyocardial implantation. Previous studies also demonstrated massive cells loss after injections due to myocardial contraction. Here we studied the dosage at which there is functional improvement, and hypothesized that cellular washout may be reduced by increasing the size of the injectate using microencapsulation.
Methods: In Experiment I, 5 groups of rats (n=9/grp) underwent coronary ligation; Grp. I had no treatment; Grp. II to V received escalating 0.5x106, 1.5x106, 3x106 and 5x106 cells each. Echocardiogram was performed at baseline, 2 days and 6 weeks after surgery to measure ejection fraction ( EF) in a blinded fashion. In Experiment II, fluorescent cell-sized microspheres (10 μm) were encapsulated in Alginate-Poly-l-Lysine-Alginate microcapsules in two different sizes. Each rat received intramyocardial injection of 1x106 microspheres. In Grp. A (n=16/grp), rats received bare microspheres, Grp. B, microspheres within 200 μm microcapsules and in Grp. C, microspheres within 400 μm microcapsules were given. After 20 minutes, hearts were harvested and the microspheres retained in the myocardium quantified.
Results: In Experiment I, baseline LVEF was 71 ± 1.4%. Two days post MI, EF was 30.5± 10.1% and no statistical difference between groups. EF at 7 weeks was 30± 4.3 in Grp. I, 30.2± 9.4% in Grp. II, 53.8± 11.8% in Grp. III, 54±8.2% in Grp. IV and 52.6 ± 7.5% in Grp. V. The improvement in LVEF was statistically significant between Grps. I-II and Grps. III - V. (p< 0.05, ANOVA and Tukey’s) In Experiment II, the microspheres retention rate was 4.3 ± 3.5% (Grp. A), 16.5 ± 7.7% (Grp. B) and 13±6.3% (Grp. C). The difference between Grp. A vs B and C was statistically significant but not between Grp. B and C . (p< 0.05, ANOVA and Tukey’s)
Conclusion: We concluded that functional improvement in this animal model starts at 1.5 x106cells, but is far from optimal. Micoencapsulation increased the retention by 4 folds. Thus this study suggests that improving mechanical retention is possible by microencapsulation of donor stem cells which may facilitate functional improvement of the damaged heart.