Characterization and Functionality of Cardiac Progenitor Cells in Congenital Heart Patients

Abstract

Background Human cardiac progenitor cells (hCPCs) may promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of hCPCs in young patients with nonischemic congenital heart defects for potential use in congenital heart defect repair warrants exploration. Methods and Results Human right atrial specimens were obtained during routine congenital cardiac surgery across 3 groups: neonates (age, <30 days), infants (age, 1 month to 2 years), and children (age, >2 to ≤13 years). C-kit+ hCPCs were 3-fold higher in neonates than in children >2 years of age. hCPC proliferation was greatest during the neonatal period as evidenced by c-kit+ Ki67+ expression but decreased with age. hCPC differentiation capacity was also greatest in neonatal right atrium as evidenced by c-kit+, NKX2–5+, NOTCH1+, and NUMB+ expression. Despite the age-dependent decline in resident hCPCs, we isolated and expanded right atrium–derived CPCs from all patients (n = 103) across all ages and diagnoses using the cardiosphere method. Intact cardiospheres contained a mix of heart-derived cell subpopulations that included cardiac progenitor cells expressing c-kit+, Islet-1, and supporting cells. The number of c-kit+–expressing cells was highest in human cardiosphere-derived cells (hCDCs) grown from neonatal and infant right atrium. Furthermore, hCDCs could differentiate into diverse cardiovascular lineages by in vitro differentiation assays. Transplanted hCDCs promoted greater myocardial regeneration and functional improvement in infarcted myocardium than transplanted cardiac fibroblasts. Conclusions Resident hCPCs are most abundant in the neonatal period and rapidly decrease over time. hCDCs can be reproducibly isolated and expanded from young human myocardial samples regardless of age or diagnosis. hCPCs are functional and have potential in congenital cardiac repair.

Cellular and Molecular Characterization of Human Cardiac Stem Cells Reveals Key Features Essential for Their Function and Safety

“…It reported that the number of CSCs changed during postnatal maturation with the most abundance in neonatal period. Isolated cells had regenerative potential and they could be used as autologous cell sources for cell therapy of heart patients [8].…”

“…The candidate stem cell for transplantation must improve heart function without inducing an immune response, arrhythmias, or carcinogenesis [3]. Results of animal model studies and clinical trials suggest that transplantation of cardiac stem cells (CSCs), resident cardiac precursor cells in the heart, may be one of the best strategies to cure adult or pediatric heart diseases [4][5][6][7][8]. All CSCs populations contain most properties of stem cells: self-renewal, multi-lineage differentiation, and clonogenic potentials.…”

Endogenous Cardiac Stem Cell Therapy for Ischemic Heart Failure

“…A study by Scheubel et al also reported that aging inhibits endothelial progenitor cell mobilization in patients undergoing CABG [110]. Moreover, other researchers have suggested that aging is involved in mediating intrinsic characteristics of stem cells, such as cell growth, proliferation, differentiation, and senescence [77,[111][112][113][114]. Clearly, epidemiological studies show that heart diseases are more prevalent among the elderly population [115].…”

Hydrogels for cardiac tissue engineering

“…91 c-Kit þ CPCs can be isolated from patients with various congenital heart defects, expanded in culture and differentiated towards the cardiomyogenic lineage. 92 Recently, it was reported that c-Kit þ stem cells promoted the formation of myocardium containing a network of blood vessels 20 days after injection into the infarction site of adult rats. 93 Similarly, intravascular delivery of c-Kit þ stem cells through the coronary arteries of rats has been shown to promote myocardial regeneration and reduce infarct size in a less invasive manner compared with surgical procedures.…”