On the road to regeneration. 'Tools' and 'Routes' towards efficient cardiac cell therapy for ischemic cardiomyopathy

Cardiac regenerative medicine is a field bridging together biotechnology and surgical science. In this review, we present the explored surgical roads to cell delivery and the known effects of each delivery method on cell therapy efficiency. We also list the more recent clinical trials, exploring the safety and efficacy of delivery routes used for cardiac cell therapy approaches. There is no consensus in defining which way is the most suitable for the delivery of the different therapeutic cell types to the damaged heart tissue. In addition, it emerged that the “delivery issue” has not been systematically addressed in each clinical trial and for each and every cell type capable of cardiac repair. Cardiac damage occurring after an ischemic insult triggers a cascade of cellular events, eventually leading to heart failure through fibrosis and maladaptive remodelling. None of the pharmacological or medical interventions approved so far can rescue or reverse this phenomenon, and cardiovascular diseases are still the leading cause of death in the western world. Therefore, for nearly 20 years, regenerative medicine approaches have focused on cell therapy as a promising road to pursue, with numerous preclinical and clinical testing of cell-based therapies being studied and developed. Nonetheless, consistent clinical results are still missing to reach consensus on the most effective strategy for ischemic cardiomyopathy, based on patient selection, diagnosis and stage of the disease, therapeutic cell type, and delivery route.