Safety and Feasibility of Autologous Myoblast Transplantation in Patients With Ischemic Cardiomyopathy

Abstract

Background-Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function. Methods and Results-Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction Ͻ40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. Conclusions-These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease. (Circulation. 2005;112: 1748-1755.)

Cellular cardiomyoplasty: clinical application

“…After cell implantation an inflamatory reaction occurs with subsequent fibrosis. Clinical-pathologic studies performed after cellular CMP showed the transplanted cells were embedded within fibrosis and without neovascularization [51,59]. This histologic configuration represents a risk for micro-reentry circuits that can in-duce ectopic generation of severe ventricular arrhythmias.…”

Cell transplantation for cardiac regeneration: where do we stand?

“…[41][42][43][44][45][46][47] The first phase II, multicentre, double-blind, placebo-controlled, doseranging, randomised study using myoblast transplantation as an adjunct to CABG, the MAGIC trial, was recently stopped because of lack of efficacy. Preliminary results from this trial suggest a modest increase in ejection fraction, as assessed by nuclear imaging and a reduction in left ventricular volumes.…”

“…48 The final results of this trial have not yet been reported. Four of the phase I studies involved myoblast transplantation as an adjunct to CABG, 41,42,44,45 one involved endoventricular injections of myoblasts 46 and one study used a coronary sinus approach. 47 Generally, patients had signs of congestive heart failure class 2-3 (NYHA), with two-to three-vessel coronary disease and an ejection fraction ranging between 20 and 40%.…”

Terapia celular no tratamento da insuficiência cardíaca isquêmica

“…Estudos clínicos confirmaram a incorporação e diferenciação de mioblastos em miócitos adultos, traduzindo-se em uma melhora clínica e de fração de ejeção 17,19 . Acompanhamento por 1 e 4 anos após implante de mioblastos em tecido cicatricial de pacientes com disfunção ventricular isquêmica demonstrou resultados consistentes, com melhora de fração de ejeção e sintomas, associados a sobrevida das células enxertadas e sua diferenciação em miócitos funcionais 20,21 . A despeito da grande maioria dos estudos com mioblastos ter sido realizada em pacientes candidatos à revascularização cirúrgica, submetidos a injeções transepicárdicas, tal via tem nítidas limitações.…”