Background: While pluripotent stem cell (PSC) therapies move toward clinical and commercial applications at a rapid rate, manufacturing reproducibility and robustness are notable bottlenecks in regulatory approval. Therapeutic applications of PSCs require large cell quantities to be generated under highly robust, well-defined, and economically viable conditions. Small-scale and short-term process optimization, however, is often performed in a linear fashion that does not account for time needed to verify the bioprocess protocols and analysis methods used. Design of a reproducible and robust bioprocess should be dynamic and include a continuous effort to understand how the process will respond over time and to different stresses before transitioning into large-scale production where stresses will be amplified.
Methods: This study utilizes a baseline protocol, developed for the short-term culture of PSC aggregates in Vertical-Wheel bioreactors, to evaluate key process attributes through long-term (serial passage) suspension culture. This was done to access overall process robustness when performed with various commercially available media and cell lines. Process output variables including growth kinetics, aggregate morphology, harvest efficiency, genomic stability, and functional pluripotency were assessed through short and long-term culture.
Results: The robust nature of the expansion protocol was demonstrated over a six-day culture period where spherical aggregate formation and expansion were observed with high-fold expansions for all five commercial media tested. Profound differences in cell growth and quality were revealed only through long-term serial expansion and in-vessel dissociation operations. Some commercial media formulations tested demonstrated maintenance of cell growth rates, aggregate morphology, and high harvest recovery efficiencies through three bioreactor serial passages using multiple PSC lines. Exceptional bioprocess robustness was even demonstrated with sustained growth and quality maintenance over 10 serial bioreactor passages. However, some commercial media tested proved less equipped for serial passage cultures in bioreactors as cultures led to cell lysis during dissociation, reduction in growth rates, and a loss of aggregate morphology.
Conclusions: This study demonstrates the importance of systematic selection and testing of bioprocess input variables, with multiple bioprocess output variables through serial passages to create a truly reproducible and robust protocol for clinical and commercial PSC production using scalable bioreactor systems.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288049 | PMC |
http://dx.doi.org/10.1186/s13287-024-03819-9 | DOI Listing |
J Hazard Mater
December 2024
State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:
Aflatoxin B1 (AFB1) exposure often causes serious food safety problems and illnesses in humans and animals, even at extremely low content. Therefore, effective degradation of AFB1 is vitally significant. Biodegradation by enzymes is an effective method to eliminate hazardous toxins, but the degradation efficiency and cost of the enzyme limit its wide application.
View Article and Find Full Text PDFFront Public Health
December 2024
Department of Communication, Faculty of Modern Languages and Communication, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia.
Introduction: The role of social media in providing fitness-related health information has been widely discussed; however, there is a notable lack of research on fitness-related health information behaviors among youth within the social media context. This study aims to address this gap by integrating Self-Determination Theory (SDT)-based internal factors and external factors (social media algorithms and source credibility).
Methods: A voluntary sample of 600 participants, aged 15 to 29, was recruited.
Sci Eng Ethics
December 2024
Brain Science Institute, Tamagawa University, Machida, Japan.
The moral status of human brain organoids (HBOs) has been debated in view of the future possibility that they may acquire phenomenal consciousness. This study empirically investigates the moral sensitivity in people's intuitive judgments about actions toward conscious HBOs. The results showed that the presence/absence of pain experience in HBOs affected the judgment about the moral permissibility of actions such as creating and destroying the HBOs; however, the presence/absence of visual experience in HBOs also affected the judgment.
View Article and Find Full Text PDFFront Bioeng Biotechnol
December 2024
Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu, China.
Introduction: () infection represents a significant global health concern, exacerbated by the emergence of drug-resistant strains resulting from conventional antibiotic treatments. Consequently, the development of vaccines with both preventive and therapeutic properties has become crucial in addressing infections. The adhesin protein HpaA has demonstrated strong immunogenicity across various adjuvants and dosage forms, positioning it as a key candidate antigen for recombinant subunit vaccines against .
View Article and Find Full Text PDFFront Public Health
December 2024
School of Journalism and Communication, Beijing Normal University, Beijing, China.
Background: The COVID-19 pandemic has shown a high severity in terms of mortality, and to mitigate the impact of the COVID-19 pandemic, a great deal of reliance has been placed on vaccines with defensive effects. In the context of the transmission of hazardous Omicron variant strains, vaccine popularization and acceptance are very important to ensure world health security. Social media can spread information and increase public confidence in and acceptance of vaccines.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!