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Updated: Jun 23, 2026
Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
Characterization and functionality of cardiac progenitor cells in congenital heart patients
Rachana Mishra1, Kalpana Vijayan, Evan J Colletti
1Children's Memorial Hospital, Division of Cardiovascular-Thoracic Surgery, 2300 Children's Plaza, Chicago, IL 60614, USA.
Insights
Human cardiac progenitor cells (hCPCs) are most abundant in newborns and decrease with age. These cells, isolated as cardiosphere-derived cells (hCDCs), show potential for congenital heart defect repair.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Developmental Biology
Background:
- Human cardiac progenitor cells (hCPCs) show promise for myocardial regeneration.
- The potential of hCPCs in pediatric congenital heart defect repair requires investigation.
Purpose of the Study:
- To explore the regenerative capacity of hCPCs in young patients with congenital heart defects.
- To investigate the age-dependent changes in hCPC abundance and function.
Main Methods:
- Human right atrial specimens were collected from neonates, infants, and children undergoing cardiac surgery.
- C-kit(+) hCPCs were quantified using immunofluorescence (Ki67, NKX2-5, NOTCH1, NUMB).
- Right atrium-derived CPCs were isolated and expanded using the cardiosphere method, forming human cardiosphere-derived cells (hCDCs).
Main Results:
- hCPCs were significantly higher in neonates compared to older children, with peak proliferation and differentiation in the neonatal period.
- hCDCs could be successfully isolated and expanded from all pediatric age groups.
- hCDCs demonstrated differentiation into multiple cardiovascular lineages and promoted myocardial regeneration in vivo.
Conclusions:
- Resident hCPCs are most abundant in neonates and decline with age.
- hCDCs are a viable cell source for pediatric congenital heart repair, regardless of age or diagnosis.
- hCPCs possess functional regenerative capabilities for cardiac repair applications.
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.
