The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial

Abstract

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.

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

“…2 Several major obstacles remain to be abated: the amount of tissues to be treated may represent dozens of kilograms; immediate cell death post-injection may exceed 80%; grafted cell migration and colonization of target muscles are extremely limited. Nevertheless, transplantation of myoblasts has been considered as a possible therapeutic approach for several pathologies such as Duchenne muscular dystrophy, 3 heart failure 4 and urinary incontinence. 5 Moreover, myoblasts are not the only candidates for muscular cell therapy approaches.…”

New Strategies for Myocardial Infarction Treatment

“…Currently, the biggest obstacle regarding the use of SkMCs in clinical treatment is that the differentiated SkMCs do not express gap junction proteins, which can potentially induce arrhythmias in recipient [27] . However, this consequence was not proven in the first randomized placebo-controlled study and long-term follow up of the MI patients after skeletal myoblast transplantation [13,28] . Further large animal model studies and clinical trials of SkMCs therapy may pay more attention to the effect of this therapy on the physiological function of the heart receiving the cells.…”

Cardiac Repair Using Stem Cells Conditioned Media Based Therapy in a Rodent Model of Myocardial Infarction and Heart Failure

“…Additionally, adverse events including rhythm disturbances and teratoma/teratocarcinoma formation have been identified utilizing stem cell grafting techniques, hampering this methodology [29][30][31][32] .…”