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

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 treatm...

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Autores principales: 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
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spelling oai:doaj.org-article:9d9e9be8c2c5494da70ba9fee477fbae2021-12-02T11:53:06ZEnhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model10.1038/s41598-017-08869-z2045-2322https://doaj.org/article/9d9e9be8c2c5494da70ba9fee477fbae2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08869-zhttps://doaj.org/toc/2045-2322Abstract 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.Masashi KawamuraShigeru MiyagawaSatsuki FukushimaAtsuhiro SaitoKenji MikiShunsuke FunakoshiYoshinori YoshidaShinya YamanakaTatsuya ShimizuTeruo OkanoTakashi DaimonKoichi TodaYoshiki SawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model
description 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.
format article
author 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
author_facet 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
author_sort Masashi Kawamura
title Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model
title_short Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model
title_full Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model
title_fullStr Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model
title_full_unstemmed Enhanced Therapeutic Effects of Human iPS Cell Derived-Cardiomyocyte by Combined Cell-Sheets with Omental Flap Technique in Porcine Ischemic Cardiomyopathy Model
title_sort enhanced therapeutic effects of human ips cell derived-cardiomyocyte by combined cell-sheets with omental flap technique in porcine ischemic cardiomyopathy model
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/9d9e9be8c2c5494da70ba9fee477fbae
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