ArticleCell research2012
Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells.
Article in Cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 247 citations in OpenAlex.
- Diet and Lipidomics Mediated Regulation of Mesenchymal Stem Cell Function: Diet, Omics and Stem Cell Connection.Biomolecules · 2026Review
- ROS-Mediated Cardiomyocyte Proliferation and Myocardial Regeneration: Mechanisms and Targeted Strategies for Ischemic Heart Disease.Journal of cardiovascular development and disease · 2026Review
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- Pluripotent stem cell-based approaches for heart repair and the potential of genetic modifications.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Culture of pluripotent stem cells in microscale droplets modulates differentiation and tissue patterning towards organoids on chip.Stem cell research & therapy · 2025Article
- Epiblast-derived CX3CR1+ progenitors generate cardiovascular cells during cardiogenesis.The EMBO journal · 2025Article
- The effects of green light-emitting diode irradiation and inducer factors on the differentiation of human adipose tissue-derived mesenchymal cells into myocardial-like cells.Lasers in medical science · 2025Article
- Cathepsin K inhibition promotes efficient differentiation of human embryonic stem cells to mature cardiomyocytes by mediating glucolipid metabolism and cellular energy homeostasis.Stem cell research & therapy · 2025Article
- The Low Tumorigenic Risk and Subtypes of Cardiomyocytes Derived from Human-induced Pluripotent Stem Cells.Current stem cell research & therapy · 2025Article
- FGF4 and ascorbic acid enhance the maturation of induced cardiomyocytes by activating JAK2-STAT3 signaling.Experimental & molecular medicine · 2024Article
- Independent compartmentalization of functional, metabolic, and transcriptional maturation of hiPSC-derived cardiomyocytes.Cell reports · 2024Article
- Article
- HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells.Stem cell research & therapy · 2024Article
- Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species.Stem cell research & therapy · 2024Article
- Sex and organ specific proteomic responses to vitamin C deficiency in the brain, heart, liver, and spleen of Gulo-/- mice.PloS one · 2024Article
- iPSC-cardiomyocytes in the preclinical prediction of candidate pharmaceutical toxicity.Frontiers in pharmacology · 2024Review
- Cardiomyocyte precursors generated by direct reprogramming and molecular beacon selection attenuate ventricular remodeling after experimental myocardial infarction.Stem cell research & therapy · 2023Article
- Ascorbic acid and salvianolic acid B enhance the valproic acid and 5-azacytidinemediated cardiac differentiation of mesenchymal stem cells.Molecular biology reports · 2023Article
- Article
- Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generation of induced pluripotent stem cells (iPSCs) has opened new avenues for the investigation of heart diseases, drug screening and potential autologous cardiac regeneration. However, their application is hampered by inefficient cardiac differentiation, high interline variability, and poor maturation of iPSC-derived cardiomyocytes (iPS-CMs). To identify efficient inducers for cardiac differentiation and maturation of iPSCs and elucidate the mechanisms, we systematically screened sixteen cardiomyocyte inducers on various murine (m) iPSCs and found that only ascorbic acid (AA) consistently and robustly enhanced the cardiac differentiation of eleven lines including eight without spontaneous cardiogenic potential. We then optimized the treatment conditions and demonstrated that differentiation day 2-6, a period for the specification of cardiac progenitor cells (CPCs), was a critical time for AA to take effect. This was further confirmed by the fact that AA increased the expression of cardiovascular but not mesodermal markers. Noteworthily, AA treatment led to approximately 7.3-fold (miPSCs) and 30.2-fold (human iPSCs) augment in the yield of iPS-CMs. Such effect was attributed to a specific increase in the proliferation of CPCs via the MEK-ERK1/2 pathway by through promoting collagen synthesis. In addition, AA-induced cardiomyocytes showed better sarcomeric organization and enhanced responses of action potentials and calcium transients to β-adrenergic and muscarinic stimulations. These findings demonstrate that AA is a suitable cardiomyocyte inducer for iPSCs to improve cardiac differentiation and maturation simply, universally, and efficiently. These findings also highlight the importance of stimulating CPC proliferation by manipulating extracellular microenvironment in guiding cardiac differentiation of the pluripotent stem cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.