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

PLoS One. 2014 Jan 21;9(1):e85645. doi: 10.1371/journal.pone.0085645. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / physiology*
  • Ion Channel Gating / physiology
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / physiology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • Homeodomain Proteins
  • Ion Channels
  • Receptors, Antigen, T-Cell
  • Transcription Factors

Grants and funding

This work was partly supported by the Support Program to break the bottlenecks at R&D Systems for accelerating the practical use of Health Research Outcome, the Highway Program for the Realization of Regenerative Medicine, and a Grant-in-Aid for JSPS Fellows. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.