ArticleScientific reports2021
Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Paracrine Induction of Cardiomyogenic Differentiation in Patient-Specific MSCs Using Conditioned Medium from iPSC-CMs.Biomedicines · 2026Article
- Tumor microenvironment-driven microRNA dysregulation: Key interactions in colorectal cancer progression.World journal of gastrointestinal oncology · 2026Review
- Early multi-omic signatures and machine learning models predict cardiomyocyte differentiation efficiency and enable robust hPSC differentiation to cardiomyocytes.bioRxiv : the preprint server for biology · 2026Article
- Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning.bioRxiv : the preprint server for biology · 2025Article
- Recent Advances of Pluripotent Stem Cell-Derived Cardiomyocytes for Regenerative Medicine.Metabolites · 2025Review
- Enhancing human pluripotent stem cell differentiation to cardiomyocytes through cardiac progenitor reseeding and cryopreservation.iScience · 2025Article
- Maturation of human induced pluripotent stem cell-derived cardiomyocytes promoted by Brachyury priming.Scientific reports · 2025Article
- The importance of matrix in cardiomyogenesis: Defined substrates for maturation and chamber specificity.Matrix biology plus · 2024Article
- In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between.Biomedicines · 2024Review
- Human heart-on-a-chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC-derived cardiomyocytes.Scientific reports · 2024Article
- Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cellsWorld journal of stem cells · 2023Article
- Engineering considerations of iPSC-based personalized medicine.Biomaterials research · 2023Review
- Electric-Field-Driven Printed 3D Highly Ordered Microstructure with Cell Feature Size Promotes the Maturation of Engineered Cardiac Tissues.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Identification of Surface Antigens That Define Human Pluripotent Stem Cell-Derived PRRX1+Limb-Bud-like Mesenchymal Cells.International journal of molecular sciences · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differentiation. Previously, we established a protocol to induce hiPSC differentiation into cardiomyocytes using a defined culture medium and an initial low cell density (1% confluence) to minimize the hidden factors. Here, we investigated the key factors promoting cardiomyocyte differentiation at an initial low cell density to clarify the effects of cell density. Co-culture of hiPSCs at an initial low cell density with those at an initial high cell density showed that signals secreted from cells (auto/paracrine factors) and not cell-cell contact signals, played an important role in cardiomyocyte differentiation. Moreover, although cultures with initial low cell density showed higher expression of anti-cardiac mesoderm genes, earlier treatment with a Wnt production inhibitor efficiently suppressed the anti-cardiac mesoderm gene expression and promoted cardiomyocyte differentiation by up to 80% at an initial low cell density. These results suggest that the main effect of cell density on cardiomyocyte differentiation is inhibition of Wnt signaling at the early stage of induction, through auto/paracrine factors.
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