Lavado-García Jesús, Pérez-Rubio Pol, Cervera Laura, Gòdia Francesc
Grup d'Enginyeria Cel·lular i Bioprocessos, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193 Barcelona, Spain; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Grup d'Enginyeria Cel·lular i Bioprocessos, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193 Barcelona, Spain.
Biotechnol Adv. 2022 Nov;60:108017. doi: 10.1016/j.biotechadv.2022.108017. Epub 2022 Jul 7.
One of the main challenges in the development of bioprocesses based on cell transient expression is the commonly reported reduction of cell specific productivity at increasing cell densities. This is generally known as the cell density effect (CDE). Many efforts have been devoted to understanding the cell metabolic implications to this phenomenon in an attempt to design operational strategies to overcome it. A comprehensive analysis of the main studies regarding the CDE is provided in this work to better define the elements comprising its cause and impact. Then, examples of methodologies and approaches employed to achieve successful transient expression at high cell densities (HCD) are thoroughly reviewed. A critical assessment of the limitations of the reported studies in the understanding of the CDE is presented, covering the leading hypothesis of the molecular implications. The overall analysis of previous work on CDE may offer useful insights for further research into manufacturing of biologics.
基于细胞瞬时表达的生物工艺开发中的主要挑战之一是，普遍报道随着细胞密度增加，细胞比生产率会下降。这通常被称为细胞密度效应（CDE）。人们已经付出了很多努力来理解这种现象对细胞代谢的影响，试图设计操作策略来克服它。这项工作对有关CDE的主要研究进行了全面分析，以更好地确定构成其原因和影响的因素。然后，对用于在高细胞密度（HCD）下实现成功瞬时表达的方法和途径的实例进行了全面回顾。对已报道研究在理解CDE方面的局限性进行了批判性评估，涵盖了分子影响的主要假设。对先前关于CDE的工作的整体分析可能为生物制品制造的进一步研究提供有用的见解。
