Cardiac Muscle Engineering: Strategies to Deliver Stem Cells to the Damaged Site

Abstract

In healthy human hearts, only 10-20% of the total cells are contractile cardiomyocytes and, at the age of 25 years, no more than 1% of them are annually substituted by progenitor cells, this percentage reducing to less than 0.5% at the age of 75. In total, less than 50% of cardiomyocytes are renewed during a normal human life span [1]. For this reason, the topic of cardiac repair is among the major challenges for the tissue engineers worldwide. In fact, cardiac diseases are a predominant cause of mortality and morbidity in industrialized countries, despite the recent advancements achieved in pharmacological treatment and interventional cardiology procedures. Nonetheless, end-stage heart failure management still relies on organ transplantation as unique approach, and, notwithstanding the use of massive immunosuppressive drugs, still a percentage falling within 20%-40% of patients encounters immune rejection during the first year post-transplant [2]. Among the patients not facing severe immune rejection, almost 70% is forced to retire or reduce their working activity, their survival rate falling below 70% during the first five years post organ transplantation [3]. Last, but not least, the economic impact of cardiovascular diseases and stroke has been estimated in 2010 at $503.2 billion [4]. Currently, post-infarction myocardial revascularization protocols include the administration of raw bone marrow stem cells, while a number of clinical trials have been performed or are currently in progress in which different cell subsets are implanted in the damaged tissue by means of surgical techniques. The results of such trials are still controversial. In fact, when autologous skeletal myoblasts were injected into the heart of patients suffering from ischemic cardiomyopathy, the modest functional improvement obtained was impaired by the arising of arrhythmia events, thus requiring the adoption of a pacemaker [5]. On the other side, intracoronary administration of bone marrow mesenchymal stem cells resulted in minimal improvements in cardiac contractile function in patients with dilated cardiomyopathy [6]. These mild results were mostly ascribed to a paracrine effect exerted on host tissue, rather than to a direct contribution of stem cells to the contractile activity.