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Recent studies suggest that the mammalian heart possesses some capacity for cardiac regeneration. This regenerative capacity is primarily documented postnatally and after myocardial infarction or pressure overload. Although the cell type that mediates endogenous regeneration is unclear, cardiac stem cells might be considered as potential candidates. To determine the number of c-kit + cardiac resident cells under conditions of pressure overload, we evaluated specimens derived from n = 8 patients with pressure overloaded single right ventricles in comparison to n = 4 explanted hearts from patients with dilated cardiomyopathy and n = 14 biopsies from children after heart transplantation. The age of the patients ranged from 16 days to 19 years. For quantification of cardiac stem cells, c-kit+/mast cell tryptase-/CD45- cells were counted and expressed as percent of the total nuclei. In specimens from patients with dilated cardiomyopathy, 0.13 ± 0.09% c-kit +/mast cell tryptase-/CD45- cells were detected. However, in specimens from patients with pressure overloaded single right ventricles, the numbers of c-kit+/mast cell tryptase-/CD45- cells were significantly higher (0.41 ±0.24%, p < 0.05). Under conditions of pressure overload, the right ventricle shows an approximately three-fold increase in c-kit+/mast cell tryptase-/CD45- cardiac resident cells. Despite the fact that this increased number of c-kit+ cells is not sufficient to prevent the failing heart from congestive heart failure, understanding the mechanism that leads to an increase of presumably cardiac resident stem cells under conditions of pressure overload might help to develop new strategies to enhance endogenous repair.

DCM is the most common cardiomyopathy in childhood. Effectiveness of anticongestive therapy is limited in most cases and about one-third of children diagnosed with DCM die or receive heart transplantation within the first year after diagnosis. Cardiac stem cell transplantation has become a promising therapy to treat heart failure in adult patients. Based on these promising results, the cardiac stem cell therapy might also represent a new therapeutic option particularly in young children. The present case documents for the first time intracoronary administration of autologous bone marrow-derived progenitor cells in a critically ill two-yr-old child with severe heart failure caused by DCM. Because of progressive worsening of the clinical condition despite maximal anticongestive treatment, the decision to perform autologous stem cell therapy was made. Cardiac stem cell therapy proved to be technically feasible, was associated with improvement in cardiac function, and might represent an option before heart transplantation in children with severe heart failure.

Progenitor cells may contribute to cardiac regeneration. Here, we investigated the role of cadherins and integrins for differentiation of human adult circulating endothelial progenitor cells (EPCs) into cardiomyocytes (CM) in a co-culture system. N- and E-cadherin were expressed in EPCs and were localized at the interface between EPCs and CM. Incubation of a blocking antibody against E-cadherin reduced the expression of CM marker protein in EPCs. Blocking antibodies against N- or P-cadherin or the beta1- and beta2-integrins were not effective. These data suggested that cell-to-cell communication mediated by E-cadherin contributes to the acquirement of a cardiomyogenic phenotype of human endothelial progenitor cells.

Novel surgical strategies have dramatically improved the initial outcome of newborns with hypoplastic left heart syndrome. However, the single systemic right ventricle remains a major challenge, with limited effectiveness of pharmacologic therapy. The present case documents that the intracoronary administration of autologous bone marrow-derived progenitor cells is technically feasible in a critically ill infant with hypoplastic left heart syndrome and severe heart failure after a hybrid comprehensive stage II procedure. Cell therapy might represent an option before heart transplantation in children with single ventricle physiology presenting with severe heart failure. [Copyright &y& Elsevier]