Pediatric End-Stage Failing Hearts Demonstrate Increased Cardiac Stem Cells

Abstract

Background We sought to determine the location, expression, and characterization of cardiac stem cells (CSCs) in children with end-stage heart failure (ESHF). We hypothesized ESHF myocardium would contain an increased number of CSCs relative to age-matched healthy myocardium, and ESHF-derived CSCs would have diminished functional capacity as evidenced by reduced telomere length. Methods Tissue samples were obtained from the explanted hearts of children undergoing heart transplantation with ESHF, defined as New York Heart Association class III or IV and ejection fraction less than 0.20, and from age-matched congenital heart disease patients with normal myocardium. The expression profile of cardiac-specific stem cell markers was determined using quantitative real time polymerase chain reaction and immunofluorescence. Cardiac stem cell growth reserve was assessed with telomere length. Results There were 15 ESHF and 15 age-matched congenital heart disease patients. End-stage heart failure myocardium demonstrated increased expression of c-kit+ and islet-1+ CSCs by 2.0- and 2.5-fold, respectively, compared with myocardium from congenital heart disease patients. There was no difference in expression of c-kit+ CSCs with advancing age from infants to children in ESHF myocardium. The c-kit+ CSCs isolated from ESHF patients demonstrated significantly reduced telomere length, suggesting a diminished functional capability in these cells (8.1 ± 0.6 kbp versus 6.3 ± 0.3 kbp; p = 0.015). Conclusions End-stage heart failure myocardium demonstrated an age-independent increase in CSCs relative to healthy myocardium; however, these CSCs from ESHF patients may have diminished proliferative ability and reduced functionality as an autologous cell therapy candidate. Further investigation is necessary to determine the role of ESHF-derived CSCs within the myocardium.

Internal associations and dynamic expression of c-kit and nanog genes in ventricular remodelling induced by adriamycin

“…The results of the present study also demonstrated that c-kit and nanog were correlated with the degree of ventricular remodelling, which demonstrated that neutrophils are able to secrete a large number of inflammatory cells (27), and inhibit the expression of c-kit and nanog during early inflammation (28,29). In the present study, this pathological process was verified from the molecular and genetic level.…”

Pediatric dilated cardiomyopathy hearts display a unique gene expression profile

“…As reported by Amir et al, these cells coexpress cardiac (SERCA) and stem cell markers and have the ability to differentiate into cardiomyocytes (16). Although there is an age-dependent decline in the relative density of these cells in hearts with normal cardiac function, work by Wehman et al (19) showed an increase in cardiac stem cell numbers in end-stage pediatric HF patients when compared with congenital heart disease controls with normal cardiac function. The number of cardiac stem cells did not decline with age in children with HF, in contrast with the decline seen in age-matched controls without HF.…”

A Deep Proteome Analysis Identifies the Complete Secretome as the Functional Unit of Human Cardiac Progenitor Cells

“…Neonatal and adult c-kit + /CD45 − CPCs, nCPCs and aCPCs respectively, were isolated from RAA biopsies using our previously described protocol involving explant plating, immune-bead selection, and expansion. 26, 28–31 All tissue specimens, even those weighing between 20 to 40 mg, generated c-kit + CPCs, which were successfully grown beyond 30 days and, on average, yielded greater than 18×10 6 cells. At passage 3 (P3), nCPCs and aCPCs had similar cellular morphologies and were negative for expression of hematopoietic markers (CD34 and CD45), endothelial markers (CD31; PECAM-1), mast cell markers (tryptase), certain cardiomyocyte lineage-specific transcription factors (GATA4 and ISL1), and embryonic stem cell markers (SSEA3 and SSEA4).…”