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.

开发基于细胞瞬时表达的生物过程的主要挑战之一是通常报告的细胞比生产力随着细胞密度的增加而降低。这通常被称为细胞密度效应 (CDE)。许多努力致力于了解细胞代谢对这一现象的影响，以试图设计克服它的操作策略。本文对有关 CDE 的主要研究进行了全面分析，以更好地定义构成其原因和影响的要素。然后，彻底审查了在高细胞密度 (HCD) 下实现成功瞬时表达的方法和方法的示例。对所报道的研究在理解 CDE 方面的局限性进行了批判性评估，涵盖分子影响的主要假设。对 CDE 先前工作的总体分析可能为进一步研究生物制剂制造提供有用的见解。