Abstract 11251: Long Term Benefits of Human Embryonic Stem Cell-Derived Cardiac Progenitors Embedded Into a Fibrin Scaffold
Introduction: Cardiac commitment of cells and biomimetic scaffolds have been shown to independently improve the therapeutic efficacy of stem cells.
Hypothesis: We tested the combination of these two approaches in a rat model of myocardial infarction subjected to a prolonged follow-up.
Methods: Eighty rats underwent permanent coronary artery ligation. Five to 7 weeks after myocardial infarction, those with an echocardiographically-measured ejection fraction (EF) ≤ 55% were reoperated on and randomly allocated to receive an epicardial cell-free fibrin patch (n=25), a fibrin patch loaded with 700,000 human embryonic stem cell (ESC)-derived SSEA1+ cardiac progenitor cells (n=30) or to serve as sham-operated controls (n=25). LV function was assessed monthly until 4 months. Hearts were then processed for the assessment of fibrosis, angiogenesis and cell proliferation and the tissue content of multiple cytokines and growth factors (by qPCR). A heart failure score was then built by integrating the absolute change in LV end-systolic (LVESV) between 4 months and baseline, and the qPCR-based expression of natriuretic peptides A and B, myosin heavy chain 7 and periostin. All data were recorded and analyzed blindly.
Results: The cell-treated group yielded better functional outcomes than the sham group (p=0.002 for EF). Changes in LVESV were also markedly different as they increased in the sham and control groups (difference between 4 months and baseline: +28.08μL ± 14.65μL [mean±SEM] and +15.41 μL ± 13.36μL, respectively), whereas they decreased by 16.76μL ± 15.55μL in hearts receiving the cell-loaded fibrin patch (p=0.01 vs. sham; p=0.052 vs. controls). Angiogenesis in the border zone was significantly greater in the cell-fibrin group (p=0.006) which yielded the lowest heart failure score (p=0.04 vs sham). Outcomes of hearts receiving the acellular fibrin patch fell between the sham and treated groups. No grafted cells were found at 4 months; there was no teratoma either.
Conclusions: These data show that a fibrin scaffold loaded with cardiac progenitors results in sustained functional protection despite the lack of permanent cell engraftment and thus support a paracrinally-induced fostering of endogenous reparative responses with long-lasting effects.
Author Disclosures: P. Menasché: None. A. Bel: None. H. Nemetalla: None. V. Vanneaux: None. V. Bellamy: None. E. Robidel: None. P. Joanne: None. S. Boitard: None. M. Périer: None. A.A. Hagège: None. P. Bruneval: None. J. Larghero: None. O. Agbulut: None.
- © 2014 by American Heart Association, Inc.