In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Yu, Tao; Miyagawa, Shigeru; Miki, Kenji; Saito, Atsuhiro; Fukushima, Satsuki; Higuchi, Takahiro; Kawamura, Masashi; Kawamura, Takuji; Ito, Emiko; Kawaguchi, Naomasa; Sawa, Yoshiki; Matsuura, Nariaki

doi:10.1253/circj.cj-12-0977

Cited by 50 publications

(52 citation statements)

References 36 publications

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“…In addition, we previously demonstrated that maturation of iPS-CMs progressed after iPS-CMs were transplanted in nude rat heart. 28 Therefore, we also expect that improving environments after cell transplantation, such as avoiding delivered cell ischemia, inflammation, and immunogenic rejection, will promote in vivo differentiation of iPS-CMs and their therapeutic effects. The combination of hiPS-CM sheets and the omentum is a promising delivery method to differentiate hiPS-CMs in vivo, because the omentum at least prevents cell ischemia after transplantation and provides better environments.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Survival of Transplanted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes by the Combination of Cell Sheets With the Pedicled Omental Flap Technique in a Porcine Heart

et al. 2013

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Background— Transplantation of cardiomyocytes that are derived from human induced pluripotent stem cell–derived cardiomyocytes (hiPS-CMs) shows promise in generating new functional myocardium in situ, whereas the survival and functionality of the transplanted cells are critical in considering this therapeutic impact. Cell-sheet method has been used to transplant many functional cells; however, potential ischemia might limit cell survival. The omentum, which is known to have rich vasculature, is expected to be a source of blood supply. We hypothesized that transplantation of hiPS-CM cell sheets combined with an omentum flap may deliver a large number of functional hiPS-CMs with enhanced blood supply. Methods and Results— Retrovirally established human iPS cells were treated with Wnt signaling molecules to induce cardiomyogenic differentiation, followed by superparamagnetic iron oxide labeling. Cell sheets were created from the magnetically labeled hiPS-CMs using temperature-responsive dishes and transplanted to porcine hearts with or without the omentum flap (n=8 each). Two months after transplantation, the survival of superparamagnetic iron oxide–labeled hiPS-CMs, assessed by MRI, was significantly greater in mini-pigs with the omentum than in those without it; histologically, vascular density in the transplanted area was significantly greater in mini-pigs with the omentum than in those without it. The transplanted tissues contained abundant cardiac troponin T–positive cells surrounded by vascular-rich structures. Conclusions— The omentum flap enhanced the survival of hiPS-CMs after transplantation via increased angiogenesis, suggesting that this strategy is useful in clinical settings. The combination of hiPS-CMs and the omentum flap may be a promising technique for the development of tissue-engineered vascular-rich new myocardium in vivo.

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Section: Discussionmentioning

confidence: 99%

Enhanced Survival of Transplanted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes by the Combination of Cell Sheets With the Pedicled Omental Flap Technique in a Porcine Heart

et al. 2013

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“…After MLCK treatment, the isolated ventricular fibers from the non-transgenic control mice showed increased Mg-ATPase activity and Ca 2+ sensitivity, as indicated by a leftward shift in the force-Ca 2+ curve, heart diseases and iPSC-CMs express cardiac-specific proteins similar to neonatal cardiac myocytes. 64 However, so far there are no reports of investigations into cMLCK and MLC2 phosphorylation in iPSC-CMs.…”

Section: Physiological Role Of Mlc2 Phosphorylation In the Heartmentioning

confidence: 99%

Biochemical and Physiological Regulation of Cardiac Myocyte Contraction by Cardiac-Specific Myosin Light Chain Kinase

Tsukamoto

Kitakaze

2013

Circ J

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“…Several groups have demonstrated the differentiation of induced pluripotent stem cells-derived cardiac progenitor cells into cardiomyocytes in situ and subsequent improvement of cardiac function of diseased heart [26,27]. The mode of action is probably similar to that of spermine-treated hADMPCs.…”

Section: Discussionmentioning

confidence: 98%

Spermine Treated-Adipose Tissue-Derived Multi-Lineage Progenitor Cells Improve Left Ventricular Dysfunction in a Swine Model of Chronic Myocardial Infarction

Okura¹,

Morita²

2016

J Stem Cell Res Ther

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In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Cited by 50 publications

References 36 publications

Enhanced Survival of Transplanted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes by the Combination of Cell Sheets With the Pedicled Omental Flap Technique in a Porcine Heart

Enhanced Survival of Transplanted Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes by the Combination of Cell Sheets With the Pedicled Omental Flap Technique in a Porcine Heart

Biochemical and Physiological Regulation of Cardiac Myocyte Contraction by Cardiac-Specific Myosin Light Chain Kinase

Spermine Treated-Adipose Tissue-Derived Multi-Lineage Progenitor Cells Improve Left Ventricular Dysfunction in a Swine Model of Chronic Myocardial Infarction

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