Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells

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

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Abstract

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.

Original languageEnglish
Article numbere85645
JournalPloS one
Volume9
Issue number1
DOIs
Publication statusPublished - 2014 Jan 21

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Seki, T., Yuasa, S., Kusumoto, D., Kunitomi, A., Saito, Y., Tohyama, S., Yae, K., Kishino, Y., Okada, M., Hashimoto, H., Takei, M., Egashira, T., Kodaira, M., Kuroda, Y., Tanaka, A., Okata, S., Suzuki, T., Murata, M., Fujita, J., & Fukuda, K. (2014). Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells. PloS one, 9(1), [e85645]. https://doi.org/10.1371/journal.pone.0085645