Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up

Gavira, Juán José; Herreros, Jesús; Perez, Ana; Velloso, María José García; Barba, Joaquín; Martín-Herrero, Francisco; Cañizo, Consuelo del; Martin-Arnau, Ana; Martí-Climent, Josep M.; Hernández, Milagros; Lopez-Holgado, Natalia; González-Santos, José María; Martín-Luengo, Cándido; Alegría, Eduardo; Prósper, Felipe

doi:10.1016/j.jtcvs.2005.11.030

Cited by 121 publications

(57 citation statements)

References 31 publications

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“…Despite this, most preclinical studies have reported that cell transplantation improves the functional outcome in both ischaemic and nonischaemic cardiomyopathy models [1,10,21]. To account for this discrepancy, it has been hypothesised that the benefit of the procedure is not related to the addition of new donorderived contractile elements but rather to indirect effects like mechanical limitation of remodelling ("girdling" effect) or paracrine actions of the graft on the host tissue.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium

Pérez-Ilzarbe

Agbulut

Pelacho

et al. 2008

European J of Heart Fail

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117

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Background: The discrepancy between the functional improvements yielded experimentally by skeletal myoblasts (SM) transplanted in infarcted myocardium and the paucity of their long-term engraftment has raised the hypothesis of cell-mediated paracrine mechanisms. Conclusions: Our data support the paracrine hypothesis whereby myoblast-secreted factors may contribute to the beneficial effects of myogenic cell transplantation in infarcted myocardium.

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Section: Discussionmentioning

confidence: 99%

“…Nevertheless, in the specific case of skeletal myoblasts (SM), the results of several preclinical and clinical studies have shown improved functional outcomes following transplantation of these myogenic progenitors into postinfarction scars [9][10][11] (review in Ref. [12]).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium

Pérez-Ilzarbe

Agbulut

Pelacho

et al. 2008

European J of Heart Fail

Self Cite

117

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“…19 The other 3 early-phase studies of adjunct-to-coronary artery bypass myoblast injections reported variable results ranging from no 20 to few episodes 21,22 of ventricular arrhythmias. Likewise, the few catheter-based trials have yielded variable data.…”

Section: Clinical Datamentioning

confidence: 99%

“…37 Another possible confounder is the pattern of perfusion, as absent or poor anterograde or collateral filling of the infarct-related artery seems to be a powerful predictor of susceptibility to ventricular arrhythmias. 38 Of note, none of the patients in the MAGIC trial 25 underwent revascularization of the cell-treated segments, which could have increased the risk of arrhythmia, as suggested by the observation that, in the trial conducted by Gavira and associates 20 in which myoblast-transplanted areas were bypassed, there were no report of postoperative arrhythmias. Finally, more recent studies using contrast-enhanced magnetic resonance imaging have shown that the extent of myocardial tissue heterogeneity in the infarct border zone is correlated with ventricular irritability.…”

Section: Nature Of the Underlying Substratementioning

confidence: 99%

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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“…In patients, although some cases of arrhythmias have been reported, overall, an improvement in the cardiac function together with an increase in the viability and perfusion has been found in most of the clinical trials published so far [79] [76] [80][81][82][83][84][85]. Some studies like that published by Gavira et al have been successful with no cardiac arrhythmia reported after one-year follow-up [80]. In this study, cells were cultured in autologous serum instead of bovine serum, which might be associated with lower inflammation.…”

Section: Clinical Trials Using Skeletal Myoblastsmentioning

confidence: 99%

Stem Cells and Cardiac Disease: Where are We Going?

Pelacho

Prósper

2008

CSCR

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During the last 10 years we have witnessed the development of a new field in research termed Stem Cell Therapy. Classically, it was considered that cells had a limited division and differentiation ability; however, this dogma was challenged when new exciting results about cell multi/pluripotency were presented to the scientific community. It was found that cells from one adult tissue source were able to originate cells of a very different type. The possibility of transplanting these cells into damaged organs with the aim of substituting sick or dead tissue, triggered many studies to understand the plasticity of the stem cells and their potential in pathological situations. Nowadays, much more is understood about stem cells, although of course, many questions, especially about their mechanism of action, still need to be answered. Their benefit after transplantation has been shown experimentally and even clinically in some cases; however, the degree of stem cell contribution through their own differentiation into the transplanted tissue, has turned out to be generally low, and increasing evidence indicates that a trophic effect must play an important role in such a benefit. A better understanding of the paracrine mechanisms involved could be of great relevance in order to develop new therapies focused on stimulating endogenous cells. On the other hand, more sophisticated methods for cell transplantation combined with bio-engineering techniques have been devised in cardiac disease models. In this review we will try to provide a critical overview of the stem cell studies performed until now and to discuss some of the questions raised about the mechanisms that are involved in their putative reparative effect in cardiovascular diseases, and their origin.

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Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up

Cited by 121 publications

References 31 publications

Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium

Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium

Stem Cell Therapy for Heart Failure

Stem Cells and Cardiac Disease: Where are We Going?

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