Growth Behavior of Number Distributed Adherent MDCK Cells for Optimization in Microcarrier Cultures

被引:25
作者
Bock, Andreas [1 ]
Sann, Heiner [1 ]
Schulze-Horsel, Josef [1 ]
Genzel, Yvonne [1 ]
Reichl, Udo [1 ,2 ]
Moehler, Lars [2 ]
机构
[1] Max Planck Inst Dynam Complex Tech Syst, D-39106 Magdeburg, Germany
[2] Otto VonGuericke Univ Magdegurg, Lehrstuhl Bioprozesstechw, D-39106 Magdeburg, Germany
关键词
animal cells; mathematical modeling; population balance; cell attachment; contact inhibition; density-dependent growth inhibition; VERO CELLS; DISSOLVED-OXYGEN; MURINE HYBRIDOMA; MAMMALIAN-CELLS; FLAT SURFACES; METABOLISM; DENSITY; SCALE; ATTACHMENT; GLUTAMINE;
D O I
10.1002/btpr.262
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
An assay for measuring the number of adherent cells on microcarriers that is independent from dilution errors in sample preparation was used to investigate attachment dynamics and cell growth. It could be shown that the recovery of seeded cells is a Junction of the specific rates of cell attachment and cell death, and finally a function of the initial cell-to-bead ratio. An unstructured, segregated population balance model was developed that considers individual classes of microcarriers covered by 1-220 cells/bead. The model describes the distribution of initially attached cells and their growth in a microcarrier system. The model distinguishes between subpopulations of dividing and nondividing cells and describes in a detailed way cell attachment, cell growth, density-dependent growth inhibition, and basic metabolism of Madin-Darby canine kidney cells used in influenza vaccine manufacturing. To obtain a model approach that is suitable for process control applications, a reduced growth model without cell subpopulations, but with a formulation of the specific cell growth rate as a function of the initial cell distribution on microcarriers after seeding was developed. With both model approaches, the fraction of growth-inhibited cells could be predicted. Simulation results of two cultivations with a different number of initially seeded cells showed that the growth kinetics of adherent cells at the given cultivation conditions is mainly determined by the range of disparity in the initial distribution of cells on microcarriers after attachment. (C) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 25: 1717-1731, 2009
引用
收藏
页码:1717 / 1731
页数:15
相关论文
共 50 条
[1]   OBSERVATIONS ON THE SOCIAL BEHAVIOUR OF CELLS IN TISSUE CULTURE .1. SPEED OF MOVEMENT OF CHICK HEART FIBROBLASTS IN RELATION TO THEIR MUTUAL CONTACTS [J].
ABERCROMBIE, M ;
HEAYSMAN, JEM .
EXPERIMENTAL CELL RESEARCH, 1953, 5 (01) :111-131
[2]   OBSERVATIONS ON THE SOCIAL BEHAVIOUR OF CELLS IN TISSUE CULTURE .2. MONOLAYERING OF FIBROBLASTS [J].
ABERCROMBIE, M ;
HEAYSMAN, JEM .
EXPERIMENTAL CELL RESEARCH, 1954, 6 (02) :293-306
[3]   The effect of glucose and glutamine on the intracellular nucleotide pool and oxygen uptake rate of a murine hybridoma [J].
Barnabé, N ;
Butler, M .
CYTOTECHNOLOGY, 2000, 34 (1-2) :47-57
[4]  
Baserga R., 1985, BIOL CELL REPROD
[5]  
BUTLER M, 1983, J CELL SCI, V61, P351
[6]  
BUTLER M, 1982, IN VITRO CELL DEV B, V18, P213, DOI 10.1007/BF02618573
[7]   MODELING OF CONTACT-INHIBITED ANIMAL-CELL GROWTH ON FLAT SURFACES AND SPHERES [J].
CHERRY, RS ;
PAPOUTSAKIS, ET .
BIOTECHNOLOGY AND BIOENGINEERING, 1989, 33 (03) :300-305
[8]   GROWTH AND DEATH IN OVERAGITATED MICROCARRIER CELL-CULTURES [J].
CROUGHAN, MS ;
WANG, DIC .
BIOTECHNOLOGY AND BIOENGINEERING, 1989, 33 (06) :731-744
[9]  
Cruz HJ, 1999, BIOTECHNOL BIOENG, V66, P104, DOI 10.1002/(SICI)1097-0290(1999)66:2<104::AID-BIT3>3.0.CO
[10]  
2-#