Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes

Nakamura, Kenta; Neidig, Lauren E.; Yang, Xiangdong; Weber, Gerhard; El‐Nachef, Danny; Tsuchida, Hiroshi; Dupras, Sarah K.; Kalucki, Faith A.; Jayabalu, Anu; Futakuchi-Tsuchida, Akiko; Nakamura, Daisy S.; Marchianò, Silvia; Bertero, Alessandro; Robinson, Melissa; Cain, Kevin C.; Whittington, Dale; Tian, Rong; Reinecke, Hans; Pabon, Lil; Knollmann, Björn C.; Kattman, Steven J.; Thies, R. Scott; MacLellan, W. Robb; Murry, Charles E.

doi:10.1016/j.stemcr.2021.08.005

Cited by 45 publications

(31 citation statements)

References 32 publications

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“…Although arrhythmic events have not been reported by reports on in situ cardiac DR in mouse models, this risk could potentially arise from the initial immaturity of early iCMs and be minimized by reducing DR time needed for effective CFs DR into mature iCMs ( 50 ). Additionally, based on very recent findings on iPSC-CMs therapies, administration of antiarrhythmic drugs could be considered and studied to assist early DR phases, enhancing patients' safety ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

Bioengineering Methods in MicroRNA-Mediated Direct Reprogramming of Fibroblasts Into Cardiomyocytes

Paoletti

Chiono

2021

Front. Cardiovasc. Med.

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Ischemic heart disease is the major cause of mortality worldwide. Despite the most recent pharmacological progresses, cardiac regeneration is yet not possible, and heart transplantation is the only therapeutic option for end-stage heart failure. Traditional cardiac regenerative medicine approaches, such as cell therapies and tissue engineering, have failed in the obtainment of human functional cardiac tissue, mainly due to unavailability of high quantities of autologous functional cardiomyocytes (CMs), low grafting efficiency, and/or arrhythmic events. Direct reprogramming (DR) of fibroblasts into induced CMs (iCMs) has emerged as a new promising approach for myocardial regeneration by in situ transdifferentiation or providing additional CM source for cell therapy. Among available DR methods, non-viral transfection with microRNAs (miRcombo: miR-1, miR-133, miR-208, and miR-499) appears promising for future clinical translation. MiRcombo transfection of fibroblasts could be significantly improved by the development of safe nanocarriers, efficiently delivering their cargo to target cells at the required stoichiometric ratio and overall dose in due times. Newly designed in vitro 3D culture microenvironments, providing biomimetic biophysical and biochemical stimuli to miRcombo-transfected cells, significantly increase the yield of fibroblast transdifferentiation into iCMs, enhancing CM gene expression. Epigenetic regulation of gene expression programs, critical to cell lineage commitment, can also be promoted by the administration of specific anti-inflammatory and anti-fibrotic soluble factors, helping in suppressing fibroblast signature. The aim of this mini-review is to introduce the readers to a relatively unknown field of cardiac research integrating bioengineering tools as relevant for the progress of miRNA-mediated cardiac DR.

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Section: Discussionmentioning

confidence: 99%

Bioengineering Methods in MicroRNA-Mediated Direct Reprogramming of Fibroblasts Into Cardiomyocytes

Paoletti

Chiono

2021

Front. Cardiovasc. Med.

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“…As mentioned, the problem of EA looms large, although pharmacologic treatments have made recent progress. 4 Immune challenges also are formidable. Autologous induced pluripotent stem cell-derived cardiomyocyte therapies are not scalable and cannot treat acute problems like recent infarction because of manufacturing time.…”

Section: Nonstandard Abbreviations and Acronymsmentioning

confidence: 99%

Flexing Their Muscles: Maturation of Stem Cell–Derived Cardiomyocytes on Elastomeric Substrates to Enhance Cardiac Repair

Karbassi

Murry

2022

Circulation

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“…Nakamura et al reported that a combination of amiodarone and ivabradine could effectively suppress cardiac death and unstable arrhythmia, although drug treatment does not abrogate arrhythmia completely (73).…”

Section: Other Issues To Be Solved For Cardiac Regenerative Therapy Arrhythmia After Transplantation Of Hpsc-cmsmentioning

confidence: 99%

“…One of the problems of transplanting hPSC-CMs into the myocardium is the appearance of arrhythmias, such as ventricular tachycardia (VT) ( 55 – 59 , 62 , 73 ). In many cases, arrhythmia appeared ~1 month after transplantation and subsided spontaneously.…”

Section: Other Issues To Be Solved For Cardiac Regenerative Therapymentioning

confidence: 99%

“…The immaturity of hPSC-CMs, and contamination of pacemaker cells and non-CMs might be responsible for arrhythmia. Nakamura et al reported that a combination of amiodarone and ivabradine could effectively suppress cardiac death and unstable arrhythmia, although drug treatment does not abrogate arrhythmia completely ( 73 ).…”

Section: Other Issues To Be Solved For Cardiac Regenerative Therapymentioning

confidence: 99%

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The Present State and Future Perspectives of Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells

Soma

Morita

Kishino

et al. 2021

Front. Cardiovasc. Med.

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The number of patients with heart failure (HF) is increasing with aging in our society worldwide. Patients with HF who are resistant to medication and device therapy are candidates for heart transplantation (HT). However, the shortage of donor hearts is a serious issue. As an alternative to HT, cardiac regenerative therapy using human pluripotent stem cells (hPSCs), such as human embryonic stem cells and induced pluripotent stem cells, is expected to be realized. Differentiation of hPSCs into cardiomyocytes (CMs) is facilitated by mimicking normal heart development. To prevent tumorigenesis after transplantation, it is important to eliminate non-CMs, including residual hPSCs, and select only CMs. Among many CM selection systems, metabolic selection based on the differences in metabolism between CMs and non-CMs is favorable in terms of cost and efficacy. Large-scale culture systems have been developed because a large number of hPSC-derived CMs (hPSC-CMs) are required for transplantation in clinical settings. In large animal models, hPSC-CMs transplanted into the myocardium improved cardiac function in a myocardial infarction model. Although post-transplantation arrhythmia and immune rejection remain problems, their mechanisms and solutions are under investigation. In this manner, the problems of cardiac regenerative therapy are being solved individually. Thus, cardiac regenerative therapy with hPSC-CMs is expected to become a safe and effective treatment for HF in the near future. In this review, we describe previous studies related to hPSC-CMs and discuss the future perspectives of cardiac regenerative therapy using hPSC-CMs.

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Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes

Cited by 45 publications

References 32 publications

Bioengineering Methods in MicroRNA-Mediated Direct Reprogramming of Fibroblasts Into Cardiomyocytes

Bioengineering Methods in MicroRNA-Mediated Direct Reprogramming of Fibroblasts Into Cardiomyocytes

Flexing Their Muscles: Maturation of Stem Cell–Derived Cardiomyocytes on Elastomeric Substrates to Enhance Cardiac Repair

The Present State and Future Perspectives of Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells

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