ArticleStem cells translational medicine2020
Optimized serial expansion of human induced pluripotent stem cells using low-density inoculation to generate clinically relevant quantities in vertical-wheel bioreactors.
Article in Stem cells translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Harnessing intermediate-scale bioreactors for next-generation macrophage production and application.Nature protocols · 2026Review
- Clinical translational research on stem cell products: prospects and challenges.Signal transduction and targeted therapy · 2026Review
- Scaling-Up Vertical-Wheel Bioreactors Based on Cell Aggregate Exposure to Shear Stress and Energy Dissipation Rate.Annals of biomedical engineering · 2026Article
- Automated vertical wheel bioreactor integrated with process analytics for T-cell manufacturing.Cytotherapy · 2025Article
- Human Stem Cell-Derived Extracellular Vesicles: A Pioneering Path from Biogenesis to Cerebral Ischemic Stroke Therapy.International journal of molecular sciences · 2025Review
- Scale-down optimization of a robust, parallelizable human induced pluripotent stem cell bioprocess for high-throughput research.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- Cortical Actin Depolymerisation in 3D Cell Culture Enhances Extracellular Vesicle Secretion and Therapeutic Effects.Journal of extracellular vesicles · 2025Article
- Scale up manufacturing approach for production of human induced pluripotent stem cell-derived islets using Vertical Wheel® bioreactors.NPJ Regenerative medicine · 2025Article
- Biomanufacturing and lipidomics analysis of extracellular vesicles secreted by human blood vessel organoids in a vertical wheel bioreactor.Stem cell research & therapy · 2025Article
- Review
- Profiling biomanufactured extracellular vesicles of human forebrain spheroids in a Vertical-Wheel Bioreactor.Journal of extracellular biology · 2024Article
- Robust bioprocess design and evaluation of commercial media for the serial expansion of human induced pluripotent stem cell aggregate cultures in vertical-wheel bioreactors.Stem cell research & therapy · 2024Article
- Article
- Stochastic biological system-of-systems modelling for iPSC culture.Communications biology · 2024Article
- Extracellular vesicle biogenesis of three-dimensional human pluripotent stem cells in a novel Vertical-Wheel bioreactor.Journal of extracellular biology · 2024Article
- Suspension culture on microcarriers and as aggregates enables expansion and differentiation of pluripotent stem cells (PSCs).Cytotherapy · 2023Article
- Harnessing developmental cues for cardiomyocyte production.Development (Cambridge, England) · 2023Review
- Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner.Advanced healthcare materials · 2023Article
- Engineering considerations of iPSC-based personalized medicine.Biomaterials research · 2023Review
- Upscaling human mesenchymal stromal cell production in a novel vertical-wheel bioreactor enhances extracellular vesicle secretion and cargo profile.Bioactive materials · 2023Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and differentiation into the three germ layers of the body. Their discovery has facilitated a new era in biomedicine for understanding human development, drug screening, disease modeling, and cell therapy while reducing ethical issues and risks of immune rejection associated with traditional embryonic stem cells. Bioreactor-based processes have been the method of choice for the efficient expansion and differentiation of stem cells in controlled environments. Current protocols for the expansion of hiPSCs use horizontal impeller, paddle, or rocking wave mixing method bioreactors which require large static cell culture starting populations and achieve only moderate cell fold increases. This study focused on optimizing inoculation, agitation, oxygen, and nutrient availability for the culture of hiPSCs as aggregates in single-use, low-shear, vertical-wheel bioreactors. Under optimized conditions, we achieved an expansion of more than 30-fold in 6 days using a small starting population of cells and minimal media resources throughout. Importantly, we showed that that this optimized bioreactor expansion protocol could be replicated over four serial passages resulting in a cumulative cell expansion of 1.06E6-fold in 28 days. Cells from the final day of the serial passage were of high quality, maintaining a normal karyotype, pluripotent marker staining, and the ability to form teratomas in vivo. These findings demonstrate that a vertical-wheel bioreactor-based bioprocess can provide optimal conditions for efficient, rapid generation of high-quality hiPSCs to meet the demands for clinical manufacturing of therapeutic cell products.
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