Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration

To realize cardiac regeneration using human induced pluripotent stem cells (hiPSCs), strategies for cell preparation, tissue engineering and transplantation must be explored. Here we report a new protocol for the simultaneous induction of cardiomyocytes (CMs) and vascular cells [endothelial cells (E...

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Veröffentlicht in:Scientific reports 2014-10, Vol.4 (1), p.6716-6716, Article 6716
Hauptverfasser: Masumoto, Hidetoshi, Ikuno, Takeshi, Takeda, Masafumi, Fukushima, Hiroyuki, Marui, Akira, Katayama, Shiori, Shimizu, Tatsuya, Ikeda, Tadashi, Okano, Teruo, Sakata, Ryuzo, Yamashita, Jun K.
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container_title Scientific reports
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creator Masumoto, Hidetoshi
Ikuno, Takeshi
Takeda, Masafumi
Fukushima, Hiroyuki
Marui, Akira
Katayama, Shiori
Shimizu, Tatsuya
Ikeda, Tadashi
Okano, Teruo
Sakata, Ryuzo
Yamashita, Jun K.
description To realize cardiac regeneration using human induced pluripotent stem cells (hiPSCs), strategies for cell preparation, tissue engineering and transplantation must be explored. Here we report a new protocol for the simultaneous induction of cardiomyocytes (CMs) and vascular cells [endothelial cells (ECs)/vascular mural cells (MCs)] and generate entirely hiPSC-engineered cardiovascular cell sheets, which showed advantageous therapeutic effects in infarcted hearts. The protocol adds to a previous differentiation protocol of CMs by using stage-specific supplementation of vascular endothelial cell growth factor for the additional induction of vascular cells. Using this cell sheet technology, we successfully generated physically integrated cardiac tissue sheets (hiPSC-CTSs). HiPSC-CTS transplantation to rat infarcted hearts significantly improved cardiac function. In addition to neovascularization, we confirmed that engrafted human cells mainly consisted of CMs in >40% of transplanted rats four weeks after transplantation. Thus, our HiPSC-CTSs show promise for cardiac regenerative therapy.
doi_str_mv 10.1038/srep06716
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subjects 13/100
13/107
631/532/2064/2158
631/532/489
692/308/2171
692/699/75/230
Animals
Cardiomyocytes
Cell Differentiation - genetics
Endothelial cells
Endothelial Cells - cytology
Endothelial Cells - transplantation
Heart
Heart diseases
Heart transplantation
Humanities and Social Sciences
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - transplantation
multidisciplinary
Myocardial Infarction - pathology
Myocardial Infarction - therapy
Myocytes, Cardiac - cytology
Myocytes, Cardiac - transplantation
Pluripotency
Rats
Regeneration
Rodents
Science
Stem cell transplantation
Stem cells
Supplements
Tissue Engineering
Transplantation
Vascularization
title Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration
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