Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model

细胞片与网膜瓣技术联合应用增强人类 iPS 细胞衍生心肌细胞对猪缺血性心肌病模型的治疗效果

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作者:Masashi Kawamura, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Kenji Miki, Shunsuke Funakoshi, Yoshinori Yoshida, Shinya Yamanaka, Tatsuya Shimizu, Teruo Okano, Takashi Daimon, Koichi Toda, Yoshiki Sawa

Abstract

Transplant of human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs) cell-sheet is a promising approach for treating ischemic cardiomyopathy (ICM). However, poor blood supply to the transplanted cell-sheet is a concern related to the effectiveness and durability of the treatment. Herein, we hypothesized that the combined the omentum flap might enhance survival and the therapeutic effects of hiPS-CM cell-sheet transplant for ICM treatment. Treatment by Wnt signaling molecules in hiPS cells produced hiPS-CMs, which were magnetically labeled by superparamagnetic iron oxide (SPIO), followed by culture in the thermoresponsive dishes to generate hiPS-CMs cell-sheets. A porcine ICM model included 4 groups; sham operation, omentum flap only, cell-sheet only, or combination therapy. Ejection fraction (EF) was significantly greater in the cell-sheet only and combination group compared to the other groups during the follow-up period. At 3 months, the EF of the combination group was significantly greater than that of the cell-sheet only group. Consistently, the survival rate of the SPIO-labeled hiPS-CMs, as assessed by MRI, was significantly greater in the combination group than in the cell-sheet only group. This cell delivery system would be useful in optimizing the hiPS-CM cell-sheet transplant for treating severe heart failure.

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