Autologous skeletal myoblast implantation into heart. The myologist's experiences and directions

Autologous skeletal myoblast transplantation are used to ameliorate the healing process of myocardium infarct or, hopefully, of genetic and acquired cardiomyophaties. In spite of successful animal experimentation, in the clinical settings several issues have to be addressed, e.g., the impact of delivery route, and the extent of shnrt-term and long-term survival of the injected skeletal myoblasts and of the derived myofibers, respectively. Our experimental animal studies with ablated muscle recently shown that when volume of tissue just larger than few mm 3 is concerned, muscle reconstruction is the result of successive migration waves of angioblasts and then satellite cell-derived myoblasts from the muscles surrounding the wound. This suggests that more than one implantation procedure may be necessary to fully repair large myocardium volumes. On the other hand, irreversibly denervated myofibers both in rodents and humans are able to regenerate continually (for decades, in case of humans). The recovery of muscle mass by fimctional electrical stimulation has proven to be effective in reverting long-term denervation atrophy of surviving fibers and in improving size of new generated myofibers. The passive stretches continually exerted by the beating heart could prevent degeneration and disappearance of the myofibers. The electrical stimulation could be an option to maintain the trophic state of the new myofibers developed in the myocardium, if nanotechnologybased selective contact, i.e., artificial synapses, could be designed and developed. Althongh they should be tested in humans, these new data and hypotheses may be determinant for future experimental studies on how to make skeletal myoblast implantation one of the final solutions to treat ischemic heart disease and cardiac failure.