Key result
Human T cell-derived iPSCs successfully differentiate into functional cardiomyocytes with native electrophysiological features.
Why the study?
It remained unknown whether human peripheral T cell-derived iPSCs with genomic rearrangements in the TCR gene could differentiate into functional cardiomyocytes in vitro.
T cell-derived iPSCs yield functional cardiomyocytes in vitro; extends reprogramming methods but leaves open clinical translation.
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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Seki et al. (2014) studied this question. Human T cell-derived induced pluripotent stem cells (TiPSCs) vs. Embryonic stem cells (ESCs) and fibroblast-derived iPSCs was evaluated on Cardiomyocyte morphology, gene expression, and electrophysiological function. Human T cell-derived induced pluripotent stem cells successfully differentiated into functional cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes.
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