In patients with old myocardial infarction, treatment with skeletal myoblast in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function,improvement in the viability of cardiac tissue in the infarct area and no induction of arrhythmias.
Background: Current clinical experience with cellular cardiomyoplasty (using serum bovine-cultivated myoblasts) has demonstrated significant malignant ventricular arrhythmias and sudden deaths in patients. In some ongoing clinical trials the implantation of cardioverterdefibrillator is mandatory. We have hypothesized that contact of human cells with fetal bovine serum results after 3-week fixation of animal proteins on the cell surface, representing an antigenic substrate for immunological and inflammatory adverse events.Methods and Results: Autologous myoblasts were transplanted into infarcted LV in 20 patients (90% males, mean age 62±8 years). Cells were cultivated in a complete human medium during 3 weeks, using the patients' own serum obtained from a blood sample or from plasmapheresis. Injections were performed during CABG (2.1 grafts/pt).All patients had an uneventful recovery. At a mean follow-up of 14±5 months without mortality, no malignant cardiac arrhythmias are reported. LV ejection fraction improved from 28±3% to 52:k4.7% (p = 0.03), and regional wall motion score index (WMSI) from 3.1 to 1.4 (p = 0.04) in the cell-treated segments. Myocardial viability tests showed areas of regeneration. Patients moved from mean NYHA class 2.5 to class 1.2.Conclusions: A total autologous cell culture procedure was used in cellular cardiomyoplasty reducing the risk of arrhythmia. Human-autologous-serum cell expansion avoids the risk of prion, viral or zoonoses contamination. Since patients treated with noncultivated bone marrow cells are free of arrhythmia, the bovine-culture medium seems to be responsible for this complication. Cellular cardiomyoplasty may be efficient to avoid progression of ventricular remodeling and subsequent heart failure in ischemic heart disease.
In patients with previous myocardial infarction, treatment with skeletal myoblasts in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function, improvement in viability, and perfusion of cardiac tissue and no significant incidence of arrhythmias.
Myocardial regeneration can be induced with the implantation of a variety of myogenic and angiogenic cell types. More than 150 patients have been treated with cellular cardiomyoplasty worldwide, 18 patients have been treated by our group. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit postischemic remodelling, and restore regional myocardial contractility. Techniques for skeletal myoblasts culture and ex vivo expansion using autologous patient serum (obtained from plasmapheresis) have been developed by our group. In this article we propose (1) a total autologous cell culture technique and procedures for cell delivery and (2) a clinical trial with appropriate endpoints structured to determine the efficacy of cellular cardiomyoplasty.
Cell SelectionOne of the major questions remaining concerning cellular therapy for heart failure is which cell type is appropriate for myocardial regeneration?. The following list describes the major cell types for cardiac myogenesis and angiogenesis which have been experimentally demonstrated to consent successful ex vivo cell-culture or cellselection procedures followed by intramyocardial implantation (Table 1). When skeletal myoblasts are used for cellular cardiomyoplasty the sequence of actions appears to be the following: cells transplanted into the myocardium first impact on diastolic dysfunction. Subsequently when sufficiently organized in myotubes and myofibers systolic performance improves. Implanted cells orient themselves against cardiac stress preventing thinning and dilatation of the injured region [9, 11]. However it is not certain whether improvement in left ventricular performance is mediated by increased systolic function caused by synchronus contraction of the graft, since skeletal myoblasts are known not to contract spontaneously.
Myoblasts
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