ArticleCirculation research2019
Aggregation of Child Cardiac Progenitor Cells Into Spheres Activates Notch Signaling and Improves Treatment of Right Ventricular Heart Failure.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Safety and efficacy of cell therapies in pediatric heart disease: a systematic review and meta-analysis.Stem cell research & therapy · 2020Pooled it
- Broccoli-derived nanovesicles protect against UVB-induced skin photoaging via integrated transcriptomic and proteomic reprogramming of redox and extracellular matrix homeostasis.Frontiers in cell and developmental biology · 2026Article
- Reinforcing Stromal Cell Spheroid Through Red-Light Preconditioning for Advanced Vascularization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Current advances in human-induced pluripotent stem cell-based models and therapeutic approaches for congenital heart disease.Molecular and cellular biochemistry · 2025Review
- Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation.Antioxidants (Basel, Switzerland) · 2024Review
- Cell-based therapies reverse the heart failure-altered right ventricular proteome towards a pre-disease state.Stem cell research & therapy · 2024Article
- Differential Effects of Four Canonical Notch-Activating Ligands on c-Kit+ Cardiac Progenitor Cells.International journal of molecular sciences · 2024Article
- Cell-based therapies reverse the heart failure-altered right ventricular proteome.Research square · 2024Article
- The Effect of Parent Cell Type on Small Extracellular Vesicle-Derived Vehicle Functionality.Advanced biology · 2024Article
- Myocardial Matrix Hydrogels Mitigate Negative Remodeling and Improve Function in Right Heart Failure Model.JACC. Basic to translational science · 2024Article
- Placement of an elastic, biohybrid patch in a model of right heart failure with pulmonary artery banding.Frontiers in bioengineering and biotechnology · 2024Article
- Statistical modeling of extracellular vesicle cargo to predict clinical trial outcomes for hypoplastic left heart syndrome.iScience · 2023Article
- Charting the Path: Navigating Embryonic Development to Potentially Safeguard against Congenital Heart Defects.Journal of personalized medicine · 2023Review
- Cell-based therapy to boost right ventricular function and cardiovascular performance in hypoplastic left heart syndrome: Current approaches and future directions.Seminars in perinatology · 2023Review
- Single-Cell RNA Sequencing Reveals Distinct Cardiac-Derived Stromal Cell Subpopulations.Journal of cardiovascular development and disease · 2022Article
- Comparative computational RNA analysis of cardiac-derived progenitor cells and their extracellular vesicles.Genomics · 2022Article
- Loss of cardiac myosin light chain kinase contributes to contractile dysfunction in right ventricular pressure overload.Physiological reports · 2022Article
- Article
- Bidirectional relationship between cardiac extracellular matrix and cardiac cells in ischemic heart disease.Stem cells (Dayton, Ohio) · 2021Review
- Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration.Journal of cardiovascular development and disease · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleCongenital heart disease can lead to life-threatening right ventricular (RV) heart failure. Results from clinical trials support expanding cardiac progenitor cell (CPC) based therapies. However, our recent data show that CPCs lose function as they age, starting as early as 1 year.
objectiveTo determine whether the aggregation of child (1-5-year-old) CPCs into scaffold-free spheres can improve differentiation by enhancing Notch signaling, a known regulator of CPC fate. We hypothesized that aggregated (3-dimensional [3D]) CPCs will repair RV heart failure better than monolayer (2-dimensional [2D]) CPCs. METHODS AND
resultsSpheres were produced with 1500 CPCs each using a microwell array. CPC aggregation significantly increased gene expression of Notch1 compared with 2D CPCs, accompanied by significant upregulation of cardiogenic transcription factors (GATA4, HAND1, MEF2C, NKX2.5, and TBX5) and endothelial markers (CD31, FLK1, FLT1, VWF). Blocking Notch receptor activation with the γ-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) diminished these effects. To evaluate the therapeutic improvements of CPC aggregation, RV heart failure was induced in athymic rats by pulmonary artery banding, and cells were implanted into the RV free wall. Echocardiographic measurements 28 days postimplantation showed significantly improved RV function with 3D compared with 2D CPCs. Tracking implanted CPCs via DiR (1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide)-labeling showed improved retention of 3D CPCs. Transducing 3D CPCs with Notch1-shRNA (short hairpin RNA) did not reduce retention, but significantly reduced RV functional improvements. Histological analyses showed 3D treatment reduced RV fibrosis and increased angiogenesis. Although 3D CPCs formed CD31
conclusionsSpherical aggregation improves child CPC function in a Notch-dependent manner. The strong reparative ability of CPC spheres warrants further investigation as a treatment for pediatric heart failure, especially in older children where reparative ability may be reduced.
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Registered trials
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