Skeletal myoblasts clinical trials

Most of the clinical experience gained with stem cells has involved therapy for AMI, particularly intracoronary infusion of bone marrow cells since skeletal myoblasts are too large for this purpose [133]. Table 7.2 summarizes the experience to date. In all of these trials, revascularization was performed promptly after the index myocardial infarction, and left ventricular systolic compromise was minor (in the BOOST trial, the baseline left ventricular ejection fraction [LVEF] was 50%). 

Clinical trials of skeletal myoblasts have focused on the treatment of patients with ischemic cardiomyopathy and systolic dysfunction. Overall, these trials have resulted in improved segmental contractility and global LVEF. The preferred delivery route has been surgical intramyocardial injection, and one feasibility trial of transendocardial injection has been reported in the literature so far. 

In the past 15 years, an extensive amount of preclinical data has been on the reparative potential of cell transplantation in acute and chronic myocardial injury. Since the first preclinical report of functional repair after the injection of autologous skeletal myoblasts into the injured heart in 1998 (7), a variety of cell types or combinations (Table I) have been proposed for transplantation during different stages of CVD (19). Preclinical data has been promising, and in at least one study, the amount of repair achieved with cell transplantation in HF is additive to current medical treatment (20). With the first cardiac clinical application in 2001 (8), the field rapidly moved from bench to bedside, and at present, we are gaining valuable information about the questions to ask and the early answers from both animal and human studies. To date, 19 clinical trials either in AMI (Table 2) or chronic HF have been published (21) (Table 3), including 13, where BM... 

A serious deleterious outcome associated to date primarily with myoblasts (and with thawed BM in chemotherapy patients) (50) is the incidence of cardiac electrical instability for a presumed transient period after cell delivery. These early reports of electrical instability in patients after the receipt of autologous skeletal myoblasts have led to doubts about the safety of these cells as a treatment in the injured heart. Patients who received myoblasts in the earliest clinical studies (33,38) were extremely ill patients with an expected high potential for negative electrical events. In fact, many of the patients who were included in the early trials met the Multicenter Automatic Defibrillator Implantation Trial MADIT-II criteria, which were presented after those trials began, and suggested that all patients who met those criteria be treated with AlCDs. As a result, in more recent clinical studies, many investigators have only enrolled patients who receive AlCDs... 

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