ArticleStem cell reviews and reports2014
Combining hypoxia and bioreactor hydrodynamics boosts induced pluripotent stem cell differentiation towards cardiomyocytes.
Article in Stem cell reviews and reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Review
- Evaluation of a high throughput multiparallel stirred bioreactor system using an apple cell line.Scientific reports · 2026Article
- Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis.Antioxidants (Basel, Switzerland) · 2026Review
- Development of 10 L mass culture system of human induced pluripotent stem cells with intermittent agitation using plastic fluid.Frontiers in bioengineering and biotechnology · 2025Article
- Oxygen control in bioreactor drives high yield production of functional hiPSC-like hepatocytes for advanced liver disease modelling.Scientific reports · 2024Article
- Protein-free media for cardiac differentiation of hPSCs in 2000 mL suspension culture.Stem cell research & therapy · 2024Article
- Standardized production of hPSC-derived cardiomyocyte aggregates in stirred spinner flasks.Nature protocols · 2024Article
- A novel perfusion bioreactor promotes the expansion of pluripotent stem cells in a 3D-bioprinted tissue chamber.Biofabrication · 2023Article
- Stress Factors as Possible Regulators of Pluripotent Stem Cell Survival and Differentiation.Biology · 2023Review
- Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation.Pharmaceutics · 2022Review
- Advances in Manufacturing Cardiomyocytes from Human Pluripotent Stem Cells.Annual review of chemical and biomolecular engineering · 2022Review
- Morpho-functional comparison of differentiation protocols to create iPSC-derived cardiomyocytes.Biology open · 2022Article
- Human-induced pluripotent stem cells in cardiovascular research: current approaches in cardiac differentiation, maturation strategies, and scalable production.Cardiovascular research · 2022Review
- Intermittent compressive force induces cell cycling and reduces apoptosis in embryoid bodies of mouse induced pluripotent stem cells.International journal of oral science · 2022Article
- Cardiac calcium regulation in human induced pluripotent stem cell cardiomyocytes: Implications for disease modeling and maturation.Frontiers in cell and developmental biology · 2022Review
- Insight in Hypoxia-Mimetic Agents as Potential Tools for Mesenchymal Stem Cell Priming in Regenerative Medicine.Stem cells international · 2022Review
- 3D models of dilated cardiomyopathy: Shaping the chemical, physical and topographical properties of biomaterials to mimic the cardiac extracellular matrix.Bioactive materials · 2022Review
- The role of hypoxia in stem cell regulation of the central nervous system: From embryonic development to adult proliferation.CNS neuroscience & therapeutics · 2021Review
- Critical Analysis of cGMP Large-Scale Expansion Process in Bioreactors of Human Induced Pluripotent Stem Cells in the Framework of Quality by Design.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- High density bioprocessing of human pluripotent stem cells by metabolic control and in silico modeling.Stem cells translational medicine · 2021Article
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Authors and funding
11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) hold great promise for patient-specific disease modeling, drug screening and cell therapy. However, existing protocols for CM differentiation of iPSCs besides being highly dependent on the application of expensive growth factors show low reproducibility and scalability. The aim of this work was to develop a robust and scalable strategy for mass production of iPSC-derived CMs by designing a bioreactor protocol that ensures a hypoxic and mechanical environment. Murine iPSCs were cultivated as aggregates in either stirred tank or WAVE bioreactors. The effect of dissolved oxygen and mechanical forces, promoted by different hydrodynamic environments, on CM differentiation was evaluated. Combining a hypoxia culture (4 % O2 tension) with an intermittent agitation profile in stirred tank bioreactors resulted in an improvement of about 1000-fold in CM yields when compared to normoxic (20 % O2 tension) and continuously agitated cultures. Additionally, we showed for the first time that wave-induced agitation enables the differentiation of iPSCs towards CMs at faster kinetics and with higher yields (60 CMs/input iPSC). In an 11-day differentiation protocol, clinically relevant numbers of CMs (2.3 × 10(9) CMs/1 L) were produced, and CMs exhibited typical cardiac sarcomeric structures, calcium transients, electrophysiological profiles and drug responsiveness. This work describes significant advances towards scalable cardiomyocyte differentiation of murine iPSC, paving the way for the implementation of this strategy for mass production of their human counterparts and their use for cardiac repair and cardiovascular research.
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