Xie L, Wang D I
Department of Chemical Engineering, Biotechnology Process Engineering Center, Room 20A-207, Massachusetts Institute of Technology, 18 Vassar Street, Cambridge, Massachusetts 02139.
Biotechnol Bioeng. 1994 May;43(11):1164-74. doi: 10.1002/bit.260431122.
Animal cell cultivation in vitro has been studied for more than 40 years. However, the culture medium composition has not been designed on the basis of the stoichiometric nutritional demands for animal cell growth. In this article, a model was developed to study the stoichiometric demands for nutrients (including glucose, 20 amino acids, and 10 vitamins)for the synthesis of cell mass and product. The coefficients for these nutrients in the stoichiometric equation governing animal cell growth were determined based on cell composition. In addition, a detailed analysis of the nutrients' roles in the synthesis of cell mass and product was also performed. Applications of the stoichiometric analysis in animal cell cultivation, such as culture medium design, supplemental medium formulation, and feeding strategy will also be discussed. The stoichiometric analysis can be potentially employed to analyze results from animal cell cultures, to improve the performance of culture processes, and to design new process rationally. It can also help to provide a better understanding of animal cell metabolism. Simplifications on the cellular energy metabolism were made in order to simplify the model and to provide the preliminary bases to test the process performance. However, this could introduce inaccuracies for the model and results in errors in the calculations of glucose and glutamine concentrations when employed in medium design. (c) 1994 John Wiley & Sons, Inc.
动物细胞体外培养的研究已有40多年。然而,培养基的组成并非基于动物细胞生长的化学计量营养需求来设计。在本文中,开发了一个模型来研究合成细胞团和产物所需营养物质(包括葡萄糖、20种氨基酸和10种维生素)的化学计量需求。根据细胞组成确定了控制动物细胞生长的化学计量方程中这些营养物质的系数。此外,还对营养物质在细胞团和产物合成中的作用进行了详细分析。还将讨论化学计量分析在动物细胞培养中的应用,如培养基设计、补充培养基配方和补料策略。化学计量分析可潜在地用于分析动物细胞培养的结果,提高培养过程的性能,并合理设计新工艺。它还有助于更好地理解动物细胞代谢。为了简化模型并为测试过程性能提供初步依据,对细胞能量代谢进行了简化。然而,这可能会给模型带来不准确性,并在用于培养基设计时导致葡萄糖和谷氨酰胺浓度计算的误差。(c) 1994约翰威立父子公司