Abstract
Cardiac diseases represent the major cause of death worldwide. Pharmacological treatments, although very sophisticated, are not able to definitively cure cardiac diseases. Furthermore, heart transplantation has shown to be efficient, but unsustainable because of donor shortage and extremely high costs of surgery and patient follow up. Finally, cell therapy applied to the injured myocardium has demonstrated to be inadequate to integrate a sufficient number of efficient contractile cells into the cardiac architecture. Considering the further expansion of cardiac diseases related to the explosive extension of longevity, it is urgent to formulate safe and cost-effective novel strategies to treat cardiac patients, without increasing the economic and social burden on public and private insurances as well as on families. Among others, the "selective repair" of the damaged region of a organ appears as the most reliable approach in the near future. Indeed, recent evidences have suggested that adult progenitor cells can be used to fabricate ex vivo engineered cardiac tissue to be implanted into the injured myocardium. However, novel materials and procedures to fabricate bio-compatible scaffolds are necessary to cope with the peculiar heart microenvironment and functional characteristics. In principle,engineered tissues can be fabricated using biocompatible polymeric scaffolds that remain embedded in the engineered tissue or, alternatively, the scaffold can be stuck on the petri bottom and the new tissue fabricated on, and not around, it. In the latter case, the engineered tissue will be scaffoldless. The current limitation of both technologies is that the scaffold is intended as a mere cell support. Instead, the scaffold must be active part in the array of biological signals governing the formation of a new tissue. This issue is very crucial in the specific case of engineered cardiac tissues that must repeat the native architecture and function. Indeed, preliminary results have shown that specifically manipulated biomaterials can be used to fabricate scaffolds inherently able to deliver signals sensed as "biologically relevant" by cells. The manipulation of the scaffold topology and nanostructure or the use of appropriate composite materials can allow to differentiate stem cells towards the cardiac phenotype in an architectural context very similar to the native one. This new class of scaffolds are very potent in addressing the cell phenotype when fine tuned in respect to the culture medium.
Alternatively, human progenitor cells, possibly isolated from the heart of the same patient candidate to receive the cell treatment, can be used to fabricate scaffoldless tissue sheets. When leant on the heart surface used as a scaffold, the scaffoldless tissue sheets release the embedded progenitor cells that easily migrate into the myocardium differentiating in cardiomyocytes and integrating in the tissue architecture, as demonstrated by the proper connections established between the graft and host cells.