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.
Biotechnology journal
|December 1, 2023
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.
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.
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