Journal Article

Generation and Characterization of Functional Cardiomyocytes Derived from Human T Cell-Derived Induced Pluripotent Stem Cells

Kishino, Yoshikazu, Egashira, Toru, Kunitomi, Akira, Kodaira, Masaki, Seki, Tomohisa, Fukuda, Keiichi, Suzuki, Tomoyuki, Yae, Kojiro, Fujita, Jun, Saito, Yuki, Hashimoto, Hisayuki, Takei, Makoto, Kuroda, Yusuke, Kusumoto, Dai, Okada, Marina, Okata, Shinichiro, Tohyama, Shugo, Murata, Mitsushige, Yuasa, Shinsuke, Tanaka, Atsushi

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Action Potentials - physiology / Amino acids / Biology / Biomarkers - metabolism / Cardiology / Cardiomyocytes / Cell culture / Cell Differentiation / Cells, Cultured / Coronary artery disease / Disease / Embryos / Fibroblasts / Floating / Gene Expression / Genes / Heart cells / Heart diseases / Heart failure / Homeodomain Proteins - genetics / Homeodomain Proteins - metabolism / Humans / Immunohistochemistry / Induced Pluripotent Stem Cells - cytology / Induced Pluripotent Stem Cells - physiology / Inhibitory postsynaptic potentials / Ion Channel Gating - physiology / Ion channels / Ion Channels - genetics / Ion Channels - metabolism / Lymphocytes / Lymphocytes T / Medicine / Morphology / Myocytes, Cardiac - cytology / Myocytes, Cardiac - physiology / Penicillin / Physicians / Pluripotency / Polymerase chain reaction / Receptors, Antigen, T-Cell - genetics / Receptors, Antigen, T-Cell - metabolism / Stem cells / T cell receptors / T cells / T-cell receptor / T-Lymphocytes - cytology / T-Lymphocytes - physiology / Transcription Factors - genetics / Transcription Factors - metabolism / Transplantation