TY - JOUR
T1 - Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells
AU - Seki, Tomohisa
AU - Yuasa, Shinsuke
AU - Kusumoto, Dai
AU - Kunitomi, Akira
AU - Saito, Yuki
AU - Tohyama, Shugo
AU - Yae, Kojiro
AU - Kishino, Yoshikazu
AU - Okada, Marina
AU - Hashimoto, Hisayuki
AU - Takei, Makoto
AU - Egashira, Toru
AU - Kodaira, Masaki
AU - Kuroda, Yusuke
AU - Tanaka, Atsushi
AU - Okata, Shinichiro
AU - Suzuki, Tomoyuki
AU - Murata, Mitsushige
AU - Fujita, Jun
AU - Fukuda, Keiichi
PY - 2014/1/21
Y1 - 2014/1/21
N2 - Induced pluripotent stem cells (iPSCs) have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs) that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR) gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies.
AB - Induced pluripotent stem cells (iPSCs) have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs) that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR) gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies.
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U2 - 10.1371/journal.pone.0085645
DO - 10.1371/journal.pone.0085645
M3 - Article
C2 - 24465630
AN - SCOPUS:84908105780
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 1
M1 - e85645
ER -