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TLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes.
Immun Inflamm Dis
January 2025
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Background: Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or Escherichia coli-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia-reperfusion.
View Article and Find Full Text PDFHarnessing cell aggregates for enhanced adeno-associated virus manufacturing: Cultivation strategies and scale-up considerations.
Biotechnol Prog
January 2025
AdBIOPRO, VINNOVA Competence Centre for Advanced Bioproduction by Continuous Processing, Royal Institute of Technology (KTH), Stockholm, Sweden.
The possibility to produce recombinant adeno-associated virus (rAAV) by adherent HEK293T cells was studied in a stirred tank bioreactor (STR) culture of cell aggregates. A proof-of-concept of rAAV production was successfully demonstrated in a process where single cells were first expanded, then cell aggregates were formed by dilution into a different medium 1 day before triple plasmid transfection was conducted. An alternative approach for the STR inoculation using a seed taken from a high cell density perfusion (HCDP) culture was also investigated.
View Article and Find Full Text PDFProcess intensification of the baculovirus expression vector system using a perfusion process with a low multiplicity of infection at high cell concentrations.
Biotechnol Prog
January 2025
Bioprocess Engineering, Wageningen University & Research, Wageningen, The Netherlands.
The emergence of new viruses and the spread of existing pathogens necessitate efficient vaccine production methods. The baculovirus expression vector system (BEVS) is an efficient and scalable system for subunit and virus-like particle vaccine production and gene therapy vectors. However, current production processes are often limited to low cell concentrations (1-4 × 10 cells/mL) in fed-batch mode.
View Article and Find Full Text PDFBillion-Scale Expansion of Functional hiPSC-Derived Cardiomyocytes in Bioreactors Through Oxygen Control and Continuous Wnt Activation.
Adv Sci (Weinh)
January 2025
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2780901, Portugal.
Generation of upscaled quantities of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), for therapeutic or testing applications, is both expensive and time-consuming. Herein, a scalable bioprocess for hiPSC-CM expansion in stirred-tank bioreactors (STB) is developed. By combining the continuous activation of the Wnt pathway, through perfusion of CHIR99021, within a mild hypoxia environment, the expansion of hiPSC-CM as aggregates is maximized, reaching 4 billion of pure hiPSC-CM in 2L STB.
View Article and Find Full Text PDFMonitoring and optimization of the microenvironment in a gravity-driven microfluidic system placed on a slow-tilting table.
J Biosci Bioeng
January 2025
Department of Bioengineering, Nagaoka University of Technology, 1603-1 Kamitomioka-machi, Nagaoka, Niigata 940-2188, Japan; Department of Science of Technology Innovation, Nagaoka University of Technology, 1603-1, Kamitomioka-machi, Nagaoka, Niigata, 940-2188 Japan. Electronic address:
Gravity-driven microfluidic chips offer portability and flexibility in different settings because pumps and connecting tubes are unnecessary for driving fluid flow. In a previous study, human induced pluripotent stem cells were cultured using gravity-driven microfluidics, with the liquid flow rate regulated by a tilting table. However, instability in cell culture has been observed, occasionally leading to cell death owing to unknown causes.
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