Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells.
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.
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan ; Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan.
Tomohisa
T
Seki
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Shinsuke
S
Yuasa
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Dai
D
Kusumoto
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Akira
A
Kunitomi
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yuki
Y
Saito
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan ; Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan.
Shugo
S
Tohyama
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Kojiro
K
Yae
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yoshikazu
Y
Kishino
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Marina
M
Okada
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Hisayuki
H
Hashimoto
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Makoto
M
Takei
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Toru
T
Egashira
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Masaki
M
Kodaira
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yusuke
Y
Kuroda
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Atsushi
A
Tanaka
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Shinichiro
S
Okata
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Tomoyuki
T
Suzuki
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Mitsushige
M
Murata
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Jun
J
Fujita
Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Keiichi
K
Fukuda
D000200:Action Potentials / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D018398:Homeodomain Proteins; D007473:Ion Channels; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors