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Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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Bioreactors are engineered vessels designed to cultivate microorganisms under controlled conditions for industrial bioprocessing. They maintain sterility and allow precise regulation of pH, temperature, oxygen, and nutrient levels to optimize microbial growth and metabolite production. Bioreactors range from small laboratory units of 1 liter to industrial systems holding up to 500,000 liters, though only about 75% of their volume is actively used for fermentation. The remaining headspace...
Batch vs Continuous Culture01:14

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Fermentation is a foundational biotechnological process used to produce pharmaceuticals, biofuels, enzymes, and food additives. Among industrial strategies, batch and continuous fermentation are the two most widely applied. Although both rely on microbial conversion of substrates into desired products, they differ markedly in operation, productivity, and suitability for specific applications.Batch fermentation occurs in a closed system in which nutrient media and inoculum are added at the...
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Fed-batch culture is a widely used bioprocessing strategy combining aspects of batch culture with controlled substrate feeding to optimize cell growth and product formation. In this semi-closed system, nutrients are strategically added during fermentation, while the accumulated products and biomass remain within the bioreactor until the end of the operation. This controlled addition of substrates allows for better management of growth kinetics, nutrient limitation, and metabolite...
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Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
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Downstream processing begins once fermentation is complete and involves a series of steps to recover and purify products such as acids, vitamins, antibiotics, or proteins.Cell HarvestingFor example, for intracellular protein-based products, the first step is harvesting the cells. This is typically achieved using centrifugation or filtration to separate the cells from the liquid phase.Cell Disruption for Intracellular ProductsIf the target product is intracellular, the harvested cells must be...

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在料批量生物反应器中剖析细胞死亡途径.

David A Mentlak1, John Raven2, Tessa Moses3

  • 1Department of Biology, University of York, Heslington, York, UK.

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|December 1, 2023
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概括

中国仓鼠卵巢 (CHO) 细胞中的细胞死亡影响生物生产. 这项研究揭示了非亡细胞死亡途径,如帕尔塔纳托斯和铁亡,导致工业CHO细胞培养中的生命力丧失.

关键词:
在CHO细胞中.帕尔塔纳托斯 (Parthanatos) 是一个中等级的生物.灭症 (apoptosis) 是一种死亡的过程.铁性化 (ferroptosis) 是一种工业生物技术 工业生物技术

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科学领域:

  • 生物技术是生物技术.
  • 细胞生物学 细胞生物学
  • 生物制药制造业 生物制药制造业

背景情况:

  • 中国仓鼠卵巢 (CHO) 细胞对于生产生物药物,包括单克隆抗体至关重要.
  • 在CHO细胞中的细胞死亡显著影响生物制药制造过程中的产品产量和质量.
  • 亡以前被认为是生物反应器内的CHO细胞中主要的细胞死亡机制.

研究的目的:

  • 在食批量培养条件下,研究工业抗体生产的CHO细胞系中细胞死亡的发生和机制.
  • 为了确定非亡细胞死亡途径是否有助于生物制药生产期间CHO细胞的生命力丧失.

主要方法:

  • 在料批培养过程中,分析工业抗体生产的CHO细胞系中细胞活力的分析.
  • 在标准和应激条件下评估亡标记 (例如,卡斯巴酶激活).
  • 检测非亡性细胞死亡途径的标记物,特别是亡和铁亡.

主要成果:

  • 在没有显著的亡标记的标准食批量培养的末期观察到CHO细胞活力下降.
  • 只有在增加的压力条件下才能诱导细胞亡,这种情况通过caspase激活来表明.
  • 在标准食批次培养过程中检测到帕他那托斯和铁亡的标记物,这表明它们参与了生命力丧失.

结论:

  • 非细胞亡的细胞死亡途径,包括帕尔塔纳托斯和铁亡,在工业CHO细胞培养中的活力降低中发挥着重要作用.
  • 针对这些非传统的细胞死亡机制提供了一种潜在的策略,以提高细胞活力和改善CHO细胞中的生物生产.