Population balance modelling of stem cell culture in 3D suspension bioreactors

被引:13
作者
Bartolini, Edoardo [1 ]
Manoli, Harry [1 ]
Costamagna, Eleonora [1 ]
Jeyaseelan, Hari Athitha [1 ]
Hamad, Mouna [1 ]
Irhimeh, Mohammad R. [2 ,3 ]
Khademhosseini, Ali [4 ,5 ,6 ]
Abbas, Ali [1 ]
机构
[1] Univ Sydney, Sch Chem & Biomol Engn, Sydney, NSW 2006, Australia
[2] Univ Western Australia, Fac Med Dent & Hlth Sci, Perth, WA 6009, Australia
[3] Royal Perth Hosp, Cell & Tissue Therapies WA, Perth, WA 6000, Australia
[4] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Biomat Innovat Res Ctr, Biomed Engn Div,Dept Med,Brigham & Womens Hosp, Boston, MA 02139 USA
[6] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA
关键词
Stem cells; Bioreactor; Population balance; Mathematical modelling; GROWTH; DIFFERENTIATION; EXPANSION;
D O I
10.1016/j.cherd.2015.07.014
中图分类号
TQ [化学工业];
学科分类号
0817 ;
摘要
Growing and culturing stem cells in scalable quantities is of significant interest for both research and therapy. In this paper, a computational population balance model is developed and validated for the description of specified inter/intra-cellular related stem cell properties of interest (e.g. cell number, mass, size, age). The model describes the effects of extra-cellular variables; (A) bioreactor batch mode initial concentrations (substrate (1.5-5 g/l), dissolved oxygen (hypoxic (5%), normoxic (21%), and hyperoxic (35%)), (B) inoculum (3.75 x 10(4)-5.0 x 10(5) cells/ml), and (C) fed-batch mode conditions (media feed rate (10-100 ml/h) and air inlet flow rate 0.5-5l/min). The highest cell concentration achieved within the analysed simulation variable ranges is found to be approximately 1.9 x 10(6) cells/ml. Importantly, the results imply the existence of an optimum (maximum) cell concentration within the extra-cellular variable space, and identifying such optimality is non-trivial and would require a computational optimisation approach for this stem cell bioreactor process. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:125 / 134
页数:10
相关论文
共 40 条
[1]  
[Anonymous], 1932, Theoretische Biologie
[2]   Development of a perfusion fed bioreactor for embryonic stem cell-derived cardiomyocyte generation: Oxygen-mediated enhancement of cardiomyocyte output [J].
Bauwens, C ;
Yin, T ;
Dang, S ;
Peerani, R ;
Zandstra, PW .
BIOTECHNOLOGY AND BIOENGINEERING, 2005, 90 (04) :452-461
[3]  
Becker S., 2012, CELLS, V1
[4]   A modular simulation package for fed-batch fermentation:: penicillin production [J].
Birol, G ;
Ündey, C ;
Çinar, A .
COMPUTERS & CHEMICAL ENGINEERING, 2002, 26 (11) :1553-1565
[5]   Differentiation of pluripotent embryonic stem cells into cardiomyocytes [J].
Boheler, KR ;
Czyz, J ;
Tweedie, D ;
Yang, HT ;
Anisimov, SV ;
Wobus, AM .
CIRCULATION RESEARCH, 2002, 91 (03) :189-201
[6]  
Carcano S., 2010, THESIS POLITECNICO M
[7]  
Chaudhuri J., 2005, BIOREACTORS TISSUE E
[8]  
Costamagna E., 2013, MODELLING HEMATOPOIE
[9]   The Dual Arrhenius and Michaelis-Menten kinetics model for decomposition of soil organic matter at hourly to seasonal time scales [J].
Davidson, Eric A. ;
Samanta, Sudeep ;
Caramori, Samantha S. ;
Savage, Kathleen .
GLOBAL CHANGE BIOLOGY, 2012, 18 (01) :371-384
[10]   Reconstruction of the oxygen uptake and carbon dioxide evolution rates of microbial cultures at near-neutral pH during highly dynamic conditions [J].
de Jonge, L. P. ;
Heijnen, J. J. ;
van Gulik, W. M. .
BIOCHEMICAL ENGINEERING JOURNAL, 2014, 83 :42-54