Proarrhythmic risk of embryonic stem cell–derived cardiomyocyte transplantation in infarcted myocardium

Liao, Song-Yan; Liu, Yuan; Siu, Chung‐Wah; Zhang, Yuelin; Lai, Wing‐Hon; Au, Ka-Wing; Lee, Yee-Ki; Chan, Yau-Chi; Yip, Pandora Mei-Chu; Wu, Ed X.; Wu, Yin; Lau, Chu‐Pak; Tse, Gary; Tse, Hung‐Fat

doi:10.1016/j.hrthm.2010.09.006

Cited by 72 publications

(61 citation statements)

References 31 publications

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“…Though cardiac function was improved after transplantation of ES cell-derived cells, one of the major problems in the cell therapy is that the donor cells do not integrate well with the host tissue, leading to discordant functional activities between them. This may ultimately cause post-transplantation arrhythmia and poor long-term outcome [3,4], due in part to a lack of intercellular connections.…”

Section: Introductionmentioning

confidence: 99%

Coculture of Embryonic Ventricular Myocytes and Mouse Embryonic Stem Cell Enhance Intercellular Signaling by Upregulation of Connexin43

Tang

Liang

et al. 2013

Cell Physiol Biochem

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Background: Stem cell therapy has been proposed as a potential treatment strategy for ischemic cardiomyopathy in recent years. A variety of stem cells or stem cell-derived cells can potentially be used for transplantation. Despite improved cardiac function after treatment, one of the major problems is the poor integration between host and donor cells which can lead to post-transplantation arrhythmia and poor long-term outcome. Methods: In the present study, we cocultured murine embryonic stem cells (mES) with murine embryonic ventricular myocytes (mEVs) in hanging drops to assess the cellular interaction and function of mES-derived cardiomyocytes under these conditions. Results: We found that when mEVs are added to a culture system of embryonic stem cells, the number of spontaneously beating areas in embryoid bodies (EBs) increases, intercellular gap junction communication is enhanced by upregulation of Cx43 expression at the mid-developmental stage and Cx43 is distributed more orderly between cardiomyocytes. Conclusions: Our findings suggest mES-derived cardiomyocytes are able to form effective signaling pathways through coculture with mEVs which is important for providing more functional grafts for cardiac cell therapy by improving the integration between transplanted and host cells.

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Section: Introductionmentioning

confidence: 99%

Coculture of Embryonic Ventricular Myocytes and Mouse Embryonic Stem Cell Enhance Intercellular Signaling by Upregulation of Connexin43

Tang

Liang

et al. 2013

Cell Physiol Biochem

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“…Up to now, no animal study has revealed a proarrhythmic risk of cell replacement therapy using fetal cardiomyocytes, but arrhythmias could even be reduced after transplantation of fetal cardiomyocytes as compared to the transplantation of myoblasts or controls [14]. In contrast, an increase in ventricular tachyarrhythmias has been described after transplantation of cardiomyocytes derived from embryonic stem cells [15]. It was not investigated, if these cells developed mature action potential properties after transplantation or if inhomogeneous electrophysiological properties of graft and host cardiomyocytes, which were pronounced before transplantation, persisted and may have induced tachyarrhythmias.…”

Section: Electrophysiological Maturationmentioning

confidence: 99%

Time-course of the electrophysiological maturation and integration of transplanted cardiomyocytes

Halbach

Krausgrill

Hannes

et al. 2012

Journal of Molecular and Cellular Cardiology

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“…A greater understanding of these cells and the effects of reprogramming is therefore required before clinical application in regenerative medicine. Another safety concern in relation to the use of stem cells pertains to the potential proarrhythmic effects of transplanted stem cells in the host heart [89,90] . Other issues include the low efficiency of human iPSC generation using classic procedures of reprogramming, the need for safe and effective methods of cell delivery and ensuring that the transplanted cells remain in the myocardium.…”

Section: Safety Concerns When Using Ipscsmentioning

confidence: 99%

Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine

Gao²,

Yang

et al. 2015

Cardiology

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Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

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Proarrhythmic risk of embryonic stem cell–derived cardiomyocyte transplantation in infarcted myocardium

Cited by 72 publications

References 31 publications

Coculture of Embryonic Ventricular Myocytes and Mouse Embryonic Stem Cell Enhance Intercellular Signaling by Upregulation of Connexin43

Coculture of Embryonic Ventricular Myocytes and Mouse Embryonic Stem Cell Enhance Intercellular Signaling by Upregulation of Connexin43

Time-course of the electrophysiological maturation and integration of transplanted cardiomyocytes

Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine

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