Cardiac tissue engineering: a reflection after a decade of hurry

Abstract

The heart is a perfect machine whose mass is mainly composed of cardiomyocytes, but also fibroblasts, endothelial, smooth muscle, nervous, and immune cells are represented. One thousand million cardiomyocytes are estimated to be lost after myocardial infarction, their loss being responsible for the impairment in heart contractile function (Laflamme and Murry, 2005). The potential success of cardiac cell therapy relies almost completely on the ability of the implanted cells to differentiate toward mature cardiomyocytes. These cells must be able to reinforce the pumping activity of the injured heart in the absence of life-threatening arrhythmias due to electrophysiological incompatibility. These conditions can only be met if the newly formed cardiomyocytes can integrate electromechanically with the host tissue while getting appropriate vascularization from host- or donor-derived vessels. Together with the regeneration of the contractile component of the heart, attention must be paid to the search for novel methods to deliver appropriate vascularization to the ischemic areas and to the preservation of structures controlling the efficiency of blood pumping to the organism: the heart valves. Although fetal, neonatal, and adult cardiomyocytes have been tested for their actual ability to engraft diseased heart and improve its function (Dowell et al., 2003), most of the hopes in cardiac tissue regeneration relies on the possibility to use pluripotent and adult stem cells in targeted tissue engineering applications. In this respect, the set-up of protocols to obtain reprogrammed pluripotent stem cells (Takahashi and Yamanaka, 2006), a discovery awarded with the Nobel Prize in Physiology or Medicine in 2012, represents the demonstration that such advances in knowledge and technology will eventually lead to novel approaches to the treatment of incurable diseases. Unfortunately, notwithstanding a decade of intense investments, the results in terms of knowledge transferred to the clinical practice are very limited. The present issue addresses the topic of cardiac tissue regeneration from the viewpoint of stem cell biologists and tissue engineers, seeking for the most appropriate source of cells to replace dead myocardium, improve the organ structure and function, as well as exploring the most suitable delivery system for such cells. In the last couple of years a number of papers have been published on the ability of biomaterials and bio-constructs to drive the differentiation of stem cells for cardiac tissue engineering applications. Most of these studies used mesenchymal stem cells (MSCs) from bone marrow, adipose tissue or induced pluripotent stem cells (iPSCs). On the other hand, the contribution of cells derived from the heart tissues is here considered of outmost importance since these cells are believed to retain the potential to become highly differentiated cardiomyocytes.