Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias

Fernandes, Sarah; Amirault, Jean-Christophe; Lande, Gilles; Nguyen, Jean–Michel; Forest, Valérie; Bignolais, Olivier; Lamirault, Guillaume; Heudes, Didier; Orsonneau, Jean-Luc; Heymann, Marie‐Françoise; Charpentier, Flavien; Lemarchand, Patricia

doi:10.1016/j.cardiores.2005.10.003

Cited by 117 publications

(98 citation statements)

References 29 publications

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“…In a rat model of myocardial infarction, Fernandes et al 12 used programmed electrical stimulation and showed an increased inducibility of ventricular arrhythmias in myoblast-injected hearts compared with controls. Of note, however, an implantable telemetry system failed to document a difference in the number of arrhythmic episodes between myoblast-injected rats and those receiving control medium.…”

Section: Skeletal Myoblastsmentioning

confidence: 99%

“…5 However, such a hypertrophy has not been found consistently. 12 Overall, these coculture experiments have been helpful in deciphering the potential mechanisms underlying arrhythmias, but one of their limitations is the use of a 2-dimensional monolayer. The incidence of arrhythmias might actually be lower in the 3-dimensional heart because of the greater number of pathways available for propagation of electrical influxes around the localized barriers formed by engrafted cells interspersed around host cardiomyocytes.…”

Section: Skeletal Myoblastsmentioning

confidence: 99%

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Stem Cell Therapy for Heart Failure

Menasché

2009

Circulation

109

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Abstract-So far, the major safety issue raised by the use of stem cells for cardiac repair has been the occurrence of ventricular arrhythmias, particularly after skeletal myoblast transplantation. Although one cannot refute a potential intrinsic arrhythmogenicity of stem cells, primarily related to their common lack of electromechanical integration into the recipient myocardium, it is also important to recognize that patients eligible for cell replacement therapy are prone to develop arrhythmias because of their underlying ischemic heart disease. Another confounding factor is the method used for the intramyocardial delivery of the cells, which can cause enough inflammatory tissue damage to further increase ventricular irritability on top of an already high baseline level. Thus any strategy designed to minimize the risk of stem cell-associated ventricular arrhythmias should take into account, besides the cell-specific ability to appropriately couple with host cardiomyocytes, the method of cell transfer and the nature of the myocardial environment targeted for cell engraftment. A more accurate characterization of the baseline risk of arrhythmias in these patients would thus be helpful for better assessing the respective contribution of the donor cells and the host myocardium to these complications. The risk-to-benefit ratio of stem cell therapy will finally have to be revisited in light of the fact that because this baseline risk is usually high, most of these patients will in any way be fitted with an implantable defibrillator. Key Words: arrhythmia Ⅲ cells Ⅲ heart failure Ⅲ myocardial infarction Ⅲ stem cells T he clinical acceptance of any new therapy is largely based on the risk-to-benefit ratio. In the case of stem cell treatment for chronic heart failure, the clinical results have so far been marginally successful, when not negative, whereas the concern that intramyocardial delivery of cells, particularly skeletal myoblasts, could cause potentially life-threatening ventricular arrhythmias has been repeatedly raised. However, in this specific context of heart failure, the legitimate emphasis on this safety issue may have led to somewhat underscore the fact that most of the patients eligible for cell replacement therapy are at high risk of arrhythmias because of their underlying ischemic heart disease to such an extent that they are now increasingly fitted with internal cardioverterdefibrillators (ICDs). 1 The objective of the present article is thus to highlight the fact that the proarrhythmic risk of stem cell therapy may not be entirely related to the cells themselves and to show that at least 2 other factors (ie, the mode of their delivery and the nature of the target substrate) can also be important contributors to posttransplantation arrhythmias. These factors should definitely be taken into account by any strategy aimed at reducing the arrhythmic risk of stem cell therapy. Summary of Experimental Data on StemCell-Induced ArrhythmiasBasically, there are 3 major mechanisms that can cause arrhythmias: reent...

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Section: Skeletal Myoblastsmentioning

confidence: 99%

Section: Skeletal Myoblastsmentioning

confidence: 99%

Stem Cell Therapy for Heart Failure

Menasché

2009

Circulation

109

View full text Add to dashboard Cite

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“…Preclinical animal studies have demonstrated the ability for skeletal myoblasts to engraft, form myotubules and enhance cardiac function after transplantation into infarcted myocardium [15]. Unfortunately, it appears that the grafts do not couple electrically with adjacent cardiomyocytes [16] and these islands of transplanted cells with different electrophysiological properties, may serve as an arrhythmogenic substrate [17].…”

Section: Adipose and Skeletal Muscle Derived Stem Cellsmentioning

confidence: 99%

Stem Cell Therapy in Acute Myocardial Infarction

Reejhsinghani¹,

Shih²

2012

J Clin Exp Cardiolog

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Over the last several years, much headway has been made in the arena of coronary artery disease, specifically in the rapid diagnosis and revascularization therapy of acute myocardial infarction. Despite these advances however, given the natural history of acute myocardial infarction (AMI), a significant proportion of patients are left with significant morbidities by consequences of impaired left ventricular function. Stem cell therapy, which was initially introduced as a novel approach to regenerate injured cardiac myocytes, has widely been gaining popularity as a feasible strategy for repairing injured myocardial muscle tissue.Over a decade of basic and clinical research has gone into determining the effectiveness of targeted progenitor stem cell delivery in the improvement of myocardial function and cardiac physiology. Our paper is a general review of the stem cells therapy in patients that have had acute myocardial infarction. Although, much of the data thus far has been suggestive of the potential benefit of this approach in human models, a quest for a definitive answer is still underway. In the treatment of acute myocardial infarction, targeted stem cell therapy, at the very least, is a union of cellular biology and clinical cardiology, which albeit nascent in its development, has laid the framework for a clear direction into the future of cardiovascular medicine.

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“…The first relevant large-scale randomized clinical trial looking into this was the MAGIC (Myoblast Autologous Grafting in Ischemic Cardiomyopathy) trial which suggested that engraftment of unmodified skeletal myoblasts may generate arrhythmias [13,14]. However, data from more recent large trials show that ventricular arrhythmic events did not differ after intramyocardial injection of skeletal myoblasts or placebo [15].…”

Section: Arrhythmia As a Side Effect Of Cell Transplantationmentioning

confidence: 99%

Stem cells in rhythmology — Short communication

Földes

2011

IMAS

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Abstract:Use of stem cells may transform the medical therapy for acute and chronic heart disease, with a predictable impact rivalling the results of revascularization and device therapies. Many cell types have been studied recently, and promising preclinical and clinical data are available on their efficacy and safety in the setting of various disorders such as arrhythmia and conduction disease. However, there are still many hurdles to be tackled for the routine clinical application of these cells. A better understanding of the biology of stem cells will help in the design of future strategies.

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Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias

Cited by 117 publications

References 29 publications

Stem Cell Therapy for Heart Failure

Stem Cell Therapy for Heart Failure

Stem Cell Therapy in Acute Myocardial Infarction

Stem cells in rhythmology — Short communication

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