| Résumé : | Cell grafting is a potential approach to improve cardiac healing and limit the progression of heart failure, which is characterized by a rapid and irreversible loss of cardiomyocytes. Many cell types have been tested. Myoblasts, being skeletal muscle progenitors, present advantages: easiness of collection, large expansion capacity, resistance to ischemia, and autologous origin. Pre-clinical results in several animal models prompted the set-up of phase I and phase II clinical trials, therefore procedures were established for producing human myoblasts for clinical use. The long-term follow-up of the historical first phase I cohort of patients indicated that clinical status and LV function stably improved over time along with a strikingly low incidence of hospitalizations, and that the arrhythmic risk was controlled by medical therapy and/or implanted cardioverter defibrilator (ICD). Given the encouraging results, the Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) phase II trial was designed to assess the safety, efficacy, and impact on general status, of high (800x106) and low (400x106) doses of myoblasts, as compared to placebo. Ninety-seven patients received treatment as adjunct to bypass surgery, and an ICD. This double blind randomized study was conducted in 21 academic hospitals in France, Germany, Belgium, United Kingdom and Italy from 01/2003 to 02/2006. The six-month follow-up demonstrated the absence of statistically increased risk of major adverse cardiac events or ventricular arrythmias (in this small sample), the absence of significant improvement of regional or global contractility (echocardiography), and the evidence for significant reversal of remodeling, an important predictor of clinical outcome (decreased LVED and LVES volumes). This approach may represent the first generation of cell therapy products for use in cardiac failure. Research ways aim at refining the indications, improving the delivery systems, and considering associations of cell types with supporting biomaterials or growth factors. Supported by : Assistance Publique Hopitaux de Paris, Genzyme SA, AFM, Inserm. |
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