Stem cell therapy and tissue engineering for correction of congenital heart disease

Abstract

This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects.

Keywords: biomaterial; congenital heart disease; scaffold; stem cells; tissue engineering.

Figure 1

Cartoon illustrating the cardiac structural alterations in common single and complex CHD.

Figure 2

Cartoon illustrating the mechanisms of prosthetic valve degeneration. Xenogenic or allogenic valves are decellularized to reduce the risk of immune response and rejection. In addition, animal derived valves can be cross-linked with glutaraldehyde. The three main mechanisms of valve failure are structural deterioration, fibrosis and calcification, and damage by rejection from the host immune system.

Figure 3

Cartoon illustrating the promising strategy of tissue engineering based on which grafts and materials are combined with patient autologous cells and grown in vitro or in a bioreactor, in order to obtain an optimized cellularized graft that lacks of immunogenicity, thrombogenicity, and risk of calcification, while having the potential to grow in parallel with the child growth.

Figure 4

Schematic cartoon summarizing the main advantages and disadvantages of using the different synthetic or biological materials and grafts for surgical correction of CHD in children.

Figure 5

Cartoon illustrating possible future strategies for the surgical management of newborns with CHD. If CHD is diagnosed prenatally, foetal cells may be harvested and iPS generated; as an alternative, umbilical cord stem cells can be isolated at the time of birth. When diagnosis of CHD is made after birth or in babies who require a palliative surgical operation soon after birth, stem cells may be isolated from surgical cardiac leftovers. All these types of cells will allow the generation of a tissue-engineered graft endowed with growth and remodeling potential, necessary for the definitive correction of cardiac defects.