<b>Transcatheter Transplantation of Autologous Skeletal Myoblasts in Postinfarction Patients With Severe Left Ventricular Dysfunction</b>

İnce, Hüseyin; Petzsch, Michael; Rehders, Tim C.; Chatterjee, Tushar; Nienaber, Christoph

doi:10.1583/04-1386r.1

Cited by 88 publications

(32 citation statements)

References 47 publications

(54 reference statements)

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“…Experimentally, myoblasts engraft in postinfarction scars, differentiate into myotubes, and improve LV function (reviewed in Dowell et al 1 ). The consistency and robustness of these results have paved the way for the first surgical [2][3][4][5][6] or catheter-based [7][8][9] phase I trials, which have confirmed feasibility but by virtue of design could not fully evaluate efficacy and safety profiles. We therefore implemented the Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial to specifically address these issues.…”

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confidence: 99%

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial

et al. 2008

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Background-Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic. Methods and Results-This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction Յ35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; nϭ33 and nϭ34, respectively) or the placebo (nϭ30). Myoblast transfer did not improve regional or global LV function beyond that seen in control patients. The absolute change in ejection fraction (median [interquartile range]) between 6 months and baseline was 4.4% (0.2; 7.3), 3.4% (Ϫ0.3; 12.4), and 5.2% (Ϫ4.4; 11.0) in the placebo, low-dose, and high-dose groups, respectively (Pϭ0.95). However, the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group. Despite a higher number of arrhythmic events in the myoblast-treated patients, the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups. Conclusions-Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function. The increased number of early postoperative arrhythmic events after myoblast transplantation, as well as the capability of high-dose injections to revert LV remodeling, warrants further investigation.

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confidence: 99%

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial

et al. 2008

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“…Also, in vivo experiments in rats showed the same cell-dose dependency [78]. 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].…”

Section: Clinical Trials Using Skeletal Myoblastsmentioning

confidence: 82%

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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“…Although some trials failed to demonstrate a significant increase in cardiac function after cell transplantation when compared with controls, several other randomized trials showed measurable improvements that were comparable to established therapeutic regimes (Reffelmann et al, 2009). Nonrandomized, smaller-scale trials also produced variable results, ranging from no significant changes in left ventricular ejection fraction to a significant improvement, of up to a 14% increase, during the follow-up period (Strauer et al, 2002;Perin et al, 2004;Fernandez-Aviles et al, 2004;Ince et al, 2004;Strauer et al, 2005;Katritsis et al, 2005;Bartunek et al, 2005;Mocini et al, 2006;Gavira et al, 2006;Ahmadi et al, 2007;Choi et al, 2007;Klein et al, 2007;Li et al, 2007;Stamm et al, 2007;Tatsumi et al, 2007).…”

Section: Clinical Studiesmentioning

confidence: 99%

Cardiac repair and regeneration: the Rubik’s cube of cell therapy for heart disease

Boudoulas

Hatzopoulos

2009

Disease Models &Amp; Mechanisms

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Acute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic cardiomyopathy suggest that transplantation of various stem cell preparations can improve heart recovery after injury. The first clinical trials in patients produced some encouraging results, showing modest benefits. Most of the positive effects are probably because of a favorable paracrine influence of stem cells on the disease microenvironment. Stem cell therapy attenuates inflammation, reduces apoptosis of surrounding cells, induces angiogenesis, and lessens the extent of fibrosis. However, little new heart tissue is formed. The current challenge is to find ways to improve the engraftment, long-term survival and appropriate differentiation of transplanted stem cells within the cardiovascular tissue. Hence, there has been a surge of interest in pluripotent stem cells with robust cardiogenic potential, as well as in the inherent repair and regenerative mechanisms of the heart. Recent discoveries on the biology of adult stem cells could have relevance for cardiac regeneration. Here, we discuss current developments in the field of cardiac repair and regeneration, and present our ideas about the future of stem cell therapy.

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Transcatheter Transplantation of Autologous Skeletal Myoblasts in Postinfarction Patients With Severe Left Ventricular Dysfunction

Abstract: Transcatheter transplantation of autologous skeletal myoblasts for severe left ventricular dysfunction in postinfarction patients is feasible, safe, and promising. Scrutiny with randomized, double-blinded, multicenter trials appears warranted.

Cited by 88 publications

References 47 publications

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial

Stem Cells and Cardiac Disease: Where are We Going?

Cardiac repair and regeneration: the Rubik’s cube of cell therapy for heart disease

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