Abstract 15321: Enhanced Therapeutic Effects of Human iPS Cell Derived Cardiomyocyte Transplantation by the Combination of Cell Sheets With the Pedicle Omental Flap Technique in a Porcine Ischemic Cardiomyopathy Model
INTRODUCTION: Transplantation of beating cells constructed from human induced pluripotent stem cell derived cardiomyocytes(hiPS-CMs) to infarct myocardium is a promising approach for treating ischemic cardiomyopathy(ICM). However, poor blood supply to the transplanted cell sheets is a concern related to the effectiveness and durability of this treatment. The pedicle omentum flap covering the transplanted cell sheets reportedly supports survival and function of the transplanted somatic tissue-derived cells. Herein, we hypothesize that the combined pedicle omentum flap may enhance survival and the therapeutic effects of hiPS-CM sheet transplantation therapy for ICM treatment.
METHODS: Treatment by Wnt signaling molecules in retrovirally established human iPS cells produced hiPS-CMs, which were magnetically labeled by superparamagnetic iron oxide(SPIO), which was followed by cultivation in temperature-responsive dishes to generate scaffold-free hiPS-CM sheets. A porcine ICM model was induced by placing an ameroid constrictor on the LAD, followed by assignment into 4 groups: 1)sham operation(n=5), 2)omentum flap only(n=5), 3)cell sheet only(n=6), and 4)cell sheet plus an omentum flap(n=6).
RESULTS: Ejection fraction(EF) was significantly greater in the cell sheet only and cell sheet plus omentum groups compared to the omentum only and sham groups during 3 month follow-up period, as assessed by cardiac MRI. At 3 months, the EF of the cell sheet plus omentum group was significantly greater than that of the cell sheet only group(52±5% vs 45±2%; P<0.01). Consistently, the signal of the SPIO, as assessed by MRI, was significantly greater in the cell-sheet plus omentum group than the cell-sheet only group(57±13% vs 27±6%; P<0.05). Histologically, SPIO- and cTNT-positive cell counts were significantly higher in the cell-sheet plus omentum group than the cell-sheet only group. Teratoma was not identified in any of the hiPS-CM transplanted animals.
Conclusions: The pedicle omental flap covering enhanced survival of hiPS-CMs in vivo and produced longer therapeutic effects at post-transplantation in a porcine ICM model. This cell delivery system would be useful in optimizing hiPS-CM sheet transplantation therapies for treating severe heart failure.
- © 2013 by American Heart Association, Inc.