Abstract 14857: Infarcted Hearts Respond Better to Cardiac Stem Cell Therapy After Pre-treatment With a Collagen Hydrogel
Background: Cell therapy is a promising approach for repairing the injured myocardium. However, cells delivered too soon after myocardial infarction (MI) suffer from low retention and survival due to the harsh inflammatory post-MI milieu. In addition, autologous cells such as cardiac stem cells (CSCs) require time for isolation and culture prior to use, which precludes their delivery soon after MI. However, biomaterial therapy is not limited by these factors and can be applied in acute MI to limit myocardial damage. In this study, we treated the myocardium at the time of MI with a collagen matrix in order to prime the healing post-infarct environment and improve the efficacy of CSC therapy delivered late after MI.
Methods/Results: C57BL/6J mice underwent LAD ligation to induce MI. Mice were then randomized to receive intramyocardial injection of PBS or matrix treatment at 3h post-MI, followed by PBS or 5х105 eGFP-CSCs at 7d post-MI. In total, 4 groups were evaluated: 1) 3h PBS/7d PBS (n=7), 2) 3h PBS/7d CSC (n=11), 3) 3h matrix/7d PBS (n=6) and 4) 3h matrix/7d CSC (n=12). Treatment with the matrix at 3h (groups 3 and 4) improved cardiac LVEF at 1wk post-MI (42.4±2.7%) compared to PBS-treated mice (groups 1 and 2; 37.9±3.7%; p=0.0004). After 4wk, the matrix/CSC treated mice (group 4) had superior LVEF (45.3±3.9%) compared to all other groups (29.4±3.9%, 35.9±2.5% and 40.1±4.0% for groups 1, 2 and 3, respectively; p≤0.02). Immunostaining for GFP+ cells revealed 1.5-fold greater CSC retention in the myocardium of matrix pre-treated mice (p=0.04). Vascular density (# of CD31+ capillaries/FOV) in the infarct area was 2.5-fold greater in PBS/CSC mice than in PBS-treated mice (group 1; p=0.001), and increased further in the matrix/CSC group (1.4-fold vs. group 2; p=0.03). The matrix/CSC treated mice (group 4) had significantly reduced scar size (% scar/total myocardial area) (by ≥40%; p≤0.002) and better preserved ventricular wall thickness (by ≥15%; p≤0.02) compared to all other treatment groups.
Conclusion: Collagen matrix treatment in acute MI primes the injured heart to be more responsive to CSC therapy. This may constitute a plausible synergistic strategy to protect the myocardium and improve the benefits that can be achieved with cell therapy.
Author Disclosures: K. Maeda: None. G. Rafatian: None. R. Seymour: None. M. Ruel: None. D.R. Davis: None. E.J. Suuronen: None.
- © 2015 by American Heart Association, Inc.